Overview of The Management of Adults With Interstitial Lung Disease

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Overview of the management of adults with interstitial

lung disease
AUTHORS: Joyce S Lee, MD, Sydney Montesi, MD
SECTION EDITORS: Talmadge E King, Jr, MD, Kevin R Flaherty, MD, MS
DEPUTY EDITOR: Paul Dieffenbach, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2024.

This topic last updated: Feb 05, 2024.
INTRODUCTION
The diffuse parenchymal lung diseases, often collectively referred to as interstitial lung
diseases (ILDs), are a heterogeneous group of disorders that are classified together because
of similar clinical, radiologic, physiologic, or pathologic manifestations ( algorithm 1) [1-5].
The descriptive term "interstitial" reflects the pathologic appearance that the abnormality
begins in the interstitium; however, most of these disorders are also associated with
extensive alteration of alveolar and airway architecture.
Although individual treatment regimens vary across these diseases, there are common
approaches to many aspects of care, including disease monitoring, evaluation of worsening
pulmonary symptoms and comorbidities, and referral for clinical trial participation, lung
transplantation, and hospice. These common aspects of care have led to the development of
ILD specialty clinics in many tertiary care centers. An overview of shared management
strategies for patients with ILD will be reviewed here.
The approach to clinical evaluation and diagnostic work-up of ILD may be found elsewhere:
● (See "Approach to the adult with interstitial lung disease: Clinical evaluation".)
● (See "Approach to the adult with interstitial lung disease: Diagnostic testing".)
● (See "Role of bronchoalveolar lavage in diagnosis of interstitial lung disease".)
● (See "Role of lung biopsy in the diagnosis of interstitial lung disease".)
● (See "Interpretation of lung biopsy results in interstitial lung disease".)
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Details regarding specific treatment of individual ILDs are likewise described separately:
● (See "Treatment of idiopathic pulmonary fibrosis".)

● (See "Treatment and prognosis of nonspecific interstitial pneumonia".)
● (See "Hypersensitivity pneumonitis (extrinsic allergic alveolitis): Treatment, prognosis,
and prevention".)
● (See "Cryptogenic organizing pneumonia".)
● (See "Respiratory bronchiolitis-associated interstitial lung disease".)
● (See "Acute interstitial pneumonia (Hamman-Rich syndrome)".)

● (See "Treatment of pulmonary sarcoidosis: Initial approach".)
● (See "Interstitial lung disease in rheumatoid arthritis".)
● (See "Treatment and prognosis of interstitial lung disease in systemic sclerosis
(scleroderma)".)
● (See "Interstitial lung disease associated with Sjögren's disease: Management and
prognosis".)
● (See "Treatment and prognosis of interstitial lung disease in systemic sclerosis
(scleroderma)".)
● (See "Interstitial lung disease in dermatomyositis and polymyositis: Treatment".)
● (See "Sporadic lymphangioleiomyomatosis: Treatment and prognosis".)
● (See "Pulmonary Langerhans cell histiocytosis".)
ONGOING MONITORING OF PATIENTS WITH ILD
Following diagnosis, clinical follow-up of patients with ILD involves reassessment of

pulmonary symptoms, evaluation of extrapulmonary manifestations of disease, assessment
of common comorbidities, and managing complications and toxicities of pharmacologic
treatments. Based on this information, further evaluation with pulmonary function testing,
chest imaging, and other work-up are appropriate.
History and physical examination
● Pulmonary symptoms and signs – We ask patients about common symptoms in ILD,
including dyspnea, cough, sputum production, hemoptysis, and exertional tolerance.
The optimal method of assessment has not been determined, but in clinical practice
dyspnea is typically assessed by a qualitative history or simple measurements, such as
the modified Medical Research Council breathlessness scale (calculator 1) [6]. Frequent
reassessment of physical activity limitation can prevent underdiagnosis of occult
disease progression. On examination, assessment of respiratory rate, pulmonary
adventitious sounds, and oxygenation (resting and exertional) may be helpful.
● Recent ILD exacerbation or other hospitalization – ILD patients are at risk of acute
exacerbations of their underlying ILD. ILD patients often fare poorly after
hospitalization and may require pulmonary rehabilitation to regain stamina.
Hospitalizations in ILD patients for respiratory failure are associated with one-year
mortality of more than 50 percent [7,8]. Additionally, exacerbations of ILD or other
serious disease frequently result in the initiation of supplemental oxygen therapy and
consideration for new therapies or alteration of chronic therapies, including dosing of
anti-inflammatory medications for which short-interval follow-up is essential. (See
'Patients with new ground-glass changes' below and "Acute exacerbations of idiopathic
pulmonary fibrosis".)
● Nonpulmonary symptoms – Systemic and nonpulmonary symptoms may indicate

disease activity that is otherwise clinically silent. Patients with ILD who develop fevers,
chills, or weight loss may have developed an underlying infection or may have an
exacerbation of their underlying ILD. We also surveil for extrapulmonary manifestations
of connective tissue diseases or sarcoidosis in all patients with ILD, as ILD may predate
the development of extrapulmonary disease in a significant minority of patients
( table 1). (See 'Other testing' below and "Overview of extrapulmonary manifestations
of sarcoidosis" and "Clinical manifestations and diagnosis of sarcoidosis", section on
'Typical presentations' and "Approach to the adult with interstitial lung disease: Clinical
evaluation", section on 'Extrapulmonary findings of systemic disease' and "Causes,
clinical manifestations, evaluation, and diagnosis of nonspecific interstitial pneumonia",
section on 'Interstitial pneumonia with autoimmune features'.)
Patients with ILD also tolerate both reflux aspiration and dysphagia poorly. Poor sleep
quality and daytime sleepiness may be evidence of obstructive sleep apnea, which can
worsen nocturnal hypoxemia, pulmonary hypertension (PH), and reflux aspiration.
Clinical evaluation for symptoms and signs of these disorders is appropriate. (See
'Comorbidity identification and management' below.)
● Drug side effects and toxicities – Many patients with ILD require ongoing therapy
with systemic glucocorticoids, alternative immunosuppressants, and/or antifibrotic
medications. While effective in the treatment of certain ILDs, these therapies carry
significant risks of side effects and toxicities that require monitoring.
• Systemic glucocorticoids – Numerous adverse effects are associated with chronic

systemic glucocorticoid therapy, including increased risk of diabetes mellitus, skin
thinning, weight gain, adrenal suppression, glaucoma, osteoporosis, insomnia,
other neuropsychiatric effects, and increased risk of infections ( table 2). Patients
on more than 20 mg of prednisone or the equivalent should receive prophylaxis for
the prevention of Pneumocystis jiroveci pneumonia. Additional information regarding
the identification and prevention of glucocorticoid adverse effects can be found

elsewhere. (See "Major adverse effects of systemic glucocorticoids" and "Treatment
and prevention of Pneumocystis pneumonia in patients without HIV", section on
'Prophylaxis'.)
• Other immunosuppressants – Other immunosuppressant medications commonly

used in the treatment of ILD patients include azathioprine, mycophenolate,
rituximab, and tocilizumab. Azathioprine requires careful monitoring and dosing to
watch for cytopenia and nephrotoxicity. Mycophenolate is teratogenic and may lead
to cytopenia and gastrointestinal side effects. Rituximab dramatically reduces
antibody levels, which can interfere with routine vaccination efforts against
respiratory diseases. Cyclophosphamide use is rare due to its toxicity and is mainly
reserved for severe or refractory cases. It also carries a significant risk of
teratogenicity, increases the likelihood of developing malignancies, and can lead to
cytopenia and nephrotoxicity. It is important to note that all of these medications
increase the risk of both opportunistic and common respiratory infections. (See
"General toxicity of cyclophosphamide in rheumatic diseases" and "Pharmacology
and side effects of azathioprine when used in rheumatic diseases" and
"Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic
diseases" and "Rituximab: Principles of use and adverse effects in rheumatoid
arthritis".)
• Antifibrotics – For patients being considered for or who are currently using
antifibrotic therapy, monitoring of liver and kidney function is appropriate.
- Nintedanib – For those receiving nintedanib, liver function test (LFT) monitoring
is required before initiation, monthly for three months after initiation, and every
three months thereafter. Nintedanib has not been explicitly studied in those
with a creatinine clearance (CrCl) <30 mL/min; we use it in patients with kidney
impairment, but there have been reports of proteinuria and other kidney
toxicity with nintedanib and other vascular endothelial growth factor inhibitors
[9]. We also monitor drug side effects (most frequently diarrhea, nausea, and
vomiting), which may require dose reduction, temporary dose interruption, or
discontinuation. Antidiarrheal medications may be helpful in some cases. (See
"Treatment of idiopathic pulmonary fibrosis", section on 'Dose and
administration'.)
- Pirfenidone – For those receiving pirfenidone, LFTs should be monitored

monthly for the first six months after initiation, and then every three months.
Severe drug-induced liver disease has been reported, but LFT elevations are
usually reversible with dose modification or drug discontinuation. Kidney
impairment should be assessed prior to initiation of pirfenidone, and dose

reduction or slower escalation should be performed in the setting of moderately
impaired function (estimated glomerular filtration rate (eGFR) 15 to 30
mL/min/1.73 m2). Pirfenidone cannot be used in those with severe renal
impairment (CrCl <15 mL/min). Like nintedanib, pirfenidone causes
gastrointestinal side effects, but it may also cause rash, photosensitivity, and,
rarely, more severe cutaneous adverse reactions (Stevens-Johnson syndrome,
toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic
symptoms). Pirfenidone clearance may be increased and systemic exposure
decreased in cigarette smokers due to hepatic enzyme (ie, CYP1A2) induction.
Patients should be instructed to quit smoking prior to initiation of therapy and
cigarette smoking should be avoided during therapy. (See "Treatment of
idiopathic pulmonary fibrosis", section on 'Dose and administration'.)
Pulmonary function testing — There are no good data to guide the frequency of
pulmonary function testing in the absence of clinical worsening; however, it is not
uncommon to observe decline in lung function prior to worsening symptoms, particularly in
those with mild disease. Assessment of pulse oxygen saturation (SpO2) at rest or with
exertion can be used to identify a gas exchange defect. For most patients, we obtain
spirometry, diffusing capacity, and resting SpO2 every three to six months after initial
evaluation or initiation of therapy, until serial testing demonstrates stability. Thereafter,
monitoring of pulmonary function may be spaced out to every 6 to 12 months in the absence
of clinical change, depending on the clinical scenario. For patients with frailty, comorbidities,
or more moderate to severe ILD (moderately reduced diffusing capacity or forced vital
capacity [FVC]), we suggest a formal six-minute walk test with oxygen titration, along with
other pulmonary function testing to assess for resting, exertional hypoxemia, and overall
conditioning.
Chest imaging — The chest radiograph is useful in suggesting the presence of ILD, however,
the diagnostic approach to ILD relies on high-resolution computed tomography (HRCT).
Outside of the initial evaluation of the patient with ILD, we do not routinely perform chest
radiograph imaging in the absence of a salutary or deleterious change in either symptoms or
pulmonary function. One exception is in patients with asymptomatic (stage I-II) sarcoidosis,
where monitoring chest radiograph every 6 to 12 months for the first two to three years is
reasonable to assess for disease remission. For individuals with progressive or active ILD,
serial HRCT imaging is recommended at regular intervals (eg, every 6 to 12 months) to
monitor disease progression, response to treatment, or to detect complications or
comorbidities associated with ILD (such as infections or malignancies). (See "Treatment of
pulmonary sarcoidosis: Initial approach", section on 'Approach to asymptomatic patients'.)
Many patients with ILD may qualify for lung cancer screening evaluations due to smoking
history; concomitant ILD typically increases the risk of lung cancer, although this has not
been well studied in all varieties of ILD. Screening for lung cancer should be considered in
the context of the patient's disease severity and other comorbidities using a shared decision-
making process. (See "Screening for lung cancer" and "Evaluation and management of lung
cancer in patients with interstitial lung disease".)
Other testing
● Surveillance and monitoring of autoantibodies – Monitoring of autoantibodies in

patients with systemic lupus erythematosus- and anti-neutrophil cytoplasmic antibody-
associated ILD can sometimes be helpful in assessing overall disease quiescence.
Additionally, some patients with idiopathic ILD may develop positive autoantibodies
suggestive of an evolving connective tissue disease. It is unclear if autoantibodies
should be monitored over time and at what frequency. It is our practice to recheck
appropriate autoantibody panels in patients with ILD who develop new or worsening
signs or symptoms that suggest an evolving connective tissue disease.
● Surveillance for pulmonary hypertension (PH) – We routinely assess for PH with

echocardiography in cases where the diffusion capacity for carbon monoxide (DLCO) is
disproportionately reduced compared with FVC, in cases where there is symptom
progression without clear progression of the underlying ILD, and in patients at elevated
risk for PH (eg, patients with systemic sclerosis). Additional testing may be required in
patients during evaluation for lung transplantation listing.
Re-evaluating diagnosis or management options — Occasionally, new information during

clinical monitoring necessitates revisiting the initial diagnosis or changing the management
strategy. Multidisciplinary discussion between clinicians, radiologists, and pathologists has
been championed by international guidelines as the gold standard for improving diagnostic
certainty [10,11] and can guide management strategy towards anti-inflammatory,
antifibrotic, or combination therapies. Also, multidisciplinary discussion can be helpful in
determining who should undergo lung biopsy for additional diagnostic information and
which method of biopsy may be most appropriate. (See "Role of lung biopsy in the diagnosis
of interstitial lung disease".)
GENERAL CARE MEASURES FOR PATIENTS WITH ILD
Comorbidity identification and management — The care of ILD patients requires careful
attention to comorbid diseases that can contribute to worsening respiratory quality of life.
These include reflux disease, dysphagia, obstructive sleep apnea, systolic or diastolic heart
failure, coronary artery disease, pulmonary hypertension (PH), chronic obstructive
pulmonary disease (COPD), and lung cancer. We have a low threshold for work-up of these
diseases in symptomatic patients with suspicious features on clinical evaluation, pulmonary
function testing, or imaging.
Tobacco cessation — Tobacco use is a risk factor for most ILDs, and it is a causative factor
for a subset of them (eg, pulmonary Langerhans cell histiocytosis, respiratory bronchiolitis-
associated ILD, desquamative interstitial pneumonitis). For those patients who are
continuing to use tobacco, we counsel smoking cessation and offer referral to behavioral
counseling and prescriptions for pharmacotherapy. ILD clinics should have close affiliations
with local resources for smoking cessation to provide a full range of assistance for this group
of patients. (See "Overview of smoking cessation management in adults" and "Behavioral
approaches to smoking cessation" and "Pharmacotherapy for smoking cessation in adults".)
Oxygen — Patients with progressive ILD will usually develop hypoxemia requiring
supplemental oxygen, initially just with exertion and then continuously. Oxygen therapy
should be prescribed to enable maintenance of normal activity. Prompt provision of
supplemental oxygen may also prevent or delay the onset of secondary PH in hypoxemic
patients. The indications, benefits, and prescription of supplemental oxygen are discussed in
detail elsewhere. (See "Long-term supplemental oxygen therapy".)
Education and support group participation — Results from a survey regarding patients'
experience with idiopathic pulmonary fibrosis (IPF) suggest that improved education and
communication about the diagnosis and management of ILD are needed [12]. For patients
with progressive disease, part of the education should include a discussion of end-of-life
issues and advanced directives. Understanding a patient's individual preferences, beliefs,
and values is a key step toward achieving an appropriate management plan [13]. Patient
support groups can be strong sources of practical advice and emotional bolstering for
patients and their caregivers, and we actively encourage their participation.
Pulmonary rehabilitation — Although much of the data supporting pulmonary

rehabilitation come from study of patients with COPD, the American Thoracic Society also
recommends pulmonary rehabilitation for patients with ILDs based on demonstrated
improvements in exercise capacity and likely improvement in dyspnea and quality of life [14].
Several studies support the use of pulmonary rehabilitation in patients with ILD [15-24]. As
an example, in a series of 113 patients with ILD, a significant reduction in dyspnea and
improvement in six-minute walk distance were found following participation in a pulmonary
rehabilitation program [16]. (See "Pulmonary rehabilitation", section on 'Pulmonary
rehabilitation in conditions other than COPD'.)
Prevention of pulmonary infections and acute exacerbations of ILD — Pulmonary

infections are poorly tolerated in patients with more advanced or fibrotic ILD [25,26]. In
addition to the acute effect on lung function, pulmonary infection may result in an acute
exacerbation of ILD (AE-ILD), which is defined as "an acute, clinically significant respiratory
deterioration characterized by evidence of new widespread alveolar abnormalities" [27]. (See
'Patients with new ground-glass changes' below and "Acute exacerbations of idiopathic
pulmonary fibrosis".)
Given our limited understanding of the pathophysiology of acute exacerbations, the primary
focus of prevention is avoidance of respiratory infections and other lung injury. In our
practice, this typically includes:
● Vaccination against respiratory infections, including:
• Streptococcus pneumoniae, regardless of age, according to United States Centers

for Disease Control and Prevention (CDC) guidelines
• Influenza (yearly, as per the standard adult vaccination schedule) ( figure 1)
• Bordetella pertussis (every 10 years, according to the standard adult vaccination
schedule) ( figure 1)
• COVID-19 (coronavirus disease 2019), according to the age-based schedule
( table 3)
• Respiratory Syncytial Virus, in individuals 60 years of age and older
There have been several reports of acute exacerbations in patients with fibrotic ILD
following COVID-19 mRNA vaccine administration [28-31]. However, both case reports
[32-34] and clinical experience inform us that infection with COVID-19 poses a larger
risk for respiratory failure than vaccination in these patients. Until further data are
available on the relative risks of acute exacerbations with different vaccine
formulations, we continue to recommend vaccination with any approved vaccine
against COVID-19. (See "Seasonal influenza vaccination in adults" and "COVID-19:
Vaccines" and "Pneumococcal vaccination in adults" and "Respiratory syncytial virus
infection in adults", section on 'Vaccination'.)
● Early outpatient treatment of respiratory infection – Treatment includes antibiotics

for possible or verified bacterial pneumonia and oseltamivir in the setting of influenza A
infection. Patients with ILD are designated by the CDC as persons at risk for severe
COVID-19 ( table 4) and therefore qualify for prioritized access to antiviral therapies,
including nirmatrelvir/ritonavir and remdesivir. (See "Seasonal influenza in
nonpregnant adults: Treatment", section on 'Patients at risk for complications or severe
illness' and "COVID-19: Management of adults with acute illness in the outpatient
setting", section on 'Treatment with COVID-19-specific therapies'.)
● Evaluation and treatment of recurrent aspiration – Patients with ILD should be

screened clinically for gastroesophageal reflux or oropharyngeal dysphagia, with a low
threshold for formal evaluation [35]. Speech therapy to improve swallow function and
appropriate dietary interventions should be strongly encouraged. Pharmacologic

treatment of reflux disease is reasonable in patients with symptomatic
gastroesophageal reflux. Empiric treatment of reflux in asymptomatic patients is not
recommended. (See "Treatment of idiopathic pulmonary fibrosis", section on 'Empiric
treatment for asymptomatic gastroesophageal reflux'.)
● Risks of general anesthesia and mechanical ventilation – Mechanical ventilation

may worsen lung injury in patients with ILD by causing ventilator-induced lung injury;
however, aspiration into an unprotected airway also leads to airway injury and ensuing
complications. Elective procedures should be performed under local and regional
anesthesia with spontaneous ventilation rather than with mechanical ventilation, when
possible. Use of noninvasive ventilation via face mask, nasal device, or laryngeal mask
airway is not protective against lung injury and may worsen aspiration risk. If
mechanical ventilation is required, it is our practice to recommend lung protective
ventilation with use of lower tidal volume ventilation. (See "Anesthesia for patients with
interstitial lung disease or other restrictive disorders".)
Palliation of dyspnea and cough — Palliative care aims to relieve suffering at all stages of
disease and is not limited to end-of-life care [36-38]. Palliative measures (eg, facial cooling
with a fan, opioids, anxiolytics) may be helpful for patients with refractory dyspnea or cough.
Introduction of principles of palliative care for patients should be undertaken in patients with
progressive ILD, and those with advanced disease may benefit from hospice care ( table 5
and table 6). (See "Assessment and management of dyspnea in palliative care" and
"Palliative care: Overview of cough, stridor, and hemoptysis in adults" and "Palliative care for
adults with nonmalignant chronic lung disease" and 'Referral for end-of-life care' below.)
Nutrition — Although much less well studied than in COPD, weight loss and malnutrition are
also common in the setting of advanced ILD. Energy imbalance is likely due to a combination
of decreased caloric intake, deconditioning, disuse atrophy, tissue hypoxia, inflammation,
and medication effects. Based on experience with improvement in clinical outcomes in
COPD, we recommend referring ILD patients with cachexia and/or weight loss for nutritional
support. (See "Malnutrition in advanced lung disease".)
Clinical trials and research — For many patients with progressive or fibrotic ILD, future
therapies offer a larger chance of benefit than the modest impact of current management.
We encourage interested patients with these diseases to participate in clinical trials of
emerging therapies. Specific trials and registries are also available for patients with a familial
history of ILD. Inclusion and exclusion criteria for clinical trials vary, so we provide all patients
with information regarding participation in randomized clinical trials whenever appropriate
trials are available.
Clinical trial information is available at ClinicalTrials.gov.

GENERAL TREATMENT PRINCIPLES
The pharmacologic treatment of ILD typically varies based on diagnosis, predominant

imaging pattern, and pathologic features. However, we can offer a few general statements
regarding treatment of ILDs that may be useful:
● Exposure-associated ILDs – ILDs arising acutely or subacutely after an environmental

or drug exposure (drug-induced pneumonitis, acute hypersensitivity pneumonitis) are
often successfully treated primarily by removal of the exposure. As adjunctive therapy, a
limited course of anti-inflammatory treatment (typically systemic glucocorticoids) may
also be used based on the severity of disease. Despite antigen avoidance and anti-
inflammatory treatment, a proportion of patients with exposure-associated ILDs (such
as hypersensitivity pneumonitis) may develop progressive pulmonary fibrosis [39,40].
(See "Hypersensitivity pneumonitis (extrinsic allergic alveolitis): Treatment, prognosis,
and prevention", section on 'Treatment' and "Bleomycin-induced lung injury", section
on 'Treatment' and "Amiodarone pulmonary toxicity", section on 'Treatment' and
"Toxicities associated with immune checkpoint inhibitors", section on 'Pneumonitis' and
"Pulmonary toxicity associated with systemic antineoplastic therapy: Clinical
presentation, diagnosis, and treatment", section on 'Treatment'.)
● Smoking-related ILDs – For patients with ILDs that are strongly associated with active
tobacco use (eg, pulmonary Langerhans cell histiocytosis, respiratory bronchiolitis-
associated ILD, or desquamative interstitial pneumonitis), every effort should be made
to achieve smoking cessation. While some lung damage is often irreversible, these
conditions frequently improve if smoking cessation can be achieved. (See "Pulmonary
Langerhans cell histiocytosis", section on 'Treatment' and "Respiratory bronchiolitis-
associated interstitial lung disease", section on 'Initial therapy'.)
● ILDs characterized by glucocorticoid responsiveness – Cryptogenic organizing

pneumonia, acute and chronic eosinophilic pneumonia, hypersensitivity pneumonitis,
drug-induced ILD, and pulmonary sarcoidosis (with the exception of stage IV disease
( table 7)) are characterized by excellent initial response to systemic glucocorticoid
therapy and a chance of remission after systemic glucocorticoid treatment. In the
absence of contraindications to glucocorticoid therapy or extrapulmonary disease
requiring alternative treatments, this is the typical initial approach to patients with
these disorders. (See "Treatment of pulmonary sarcoidosis: Initial approach" and
"Cryptogenic organizing pneumonia", section on 'Treatment' and "Idiopathic acute
eosinophilic pneumonia", section on 'Treatment' and "Chronic eosinophilic pneumonia",
section on 'Treatment'.)
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● ILDs with accompanying extrapulmonary manifestations – For ILDs associated with

connective tissue diseases or with extrapulmonary manifestations (eg, sarcoidosis,
rheumatoid arthritis, and scleroderma), ILD management may be only a component of
maintaining overall disease control. Because of this, worsening extrapulmonary
symptoms should be carefully assessed, and may necessitate changes in therapy
despite stable pulmonary function.
APPROACH TO THE ILD PATIENT WITH WORSENING PULMONARY

SYMPTOMS
General approach and differential diagnosis — For many types of ILD, especially fibrotic
ILDs, disease progression is expected despite optimal medical management. The symptoms
of disease progression, such as cough, dyspnea, or hypoxemia, commonly overlap with other
conditions such as respiratory infection, acute decompensated heart failure, pulmonary
hypertension (PH), pulmonary embolism, or pneumothorax. Additionally, worsening
pulmonary symptoms can be triggered by acute exacerbation of the underlying disease,
drug toxicity, malignancy, anemia, coronary artery disease, and deconditioning, among
others.
For patients with worsening pulmonary symptoms, initial diagnostic steps usually include
pulmonary function testing and imaging such as a chest radiograph or computed
tomography (CT), tailored based on the presenting symptoms. Additional evaluation and
treatment are based on the results of this initial work-up, as outlined below.
Patients with progressive fibrotic changes or worsening restriction — The development

of progressive fibrosis and worsening restriction is expected in the patient with idiopathic
pulmonary fibrosis (IPF) and may lead to initiation or adjustment in treatment. (See
"Treatment of idiopathic pulmonary fibrosis", section on 'Medical therapies'.)
However, patients with non-IPF ILDs can also develop a progressive fibrosing phenotype with
a prognosis approaching that of patients with IPF [41]. Those with more extensive fibrosis
(≥20 percent of total lung volume) or usual interstitial pneumonia CT imaging pattern are
more likely to progress than patients without these features [40,42].
Attempts to collectively study this group of patients at high risk for poor prognosis led to
clinical trials with overlapping but different definitions [43-45]. In 2022, a diagnostic
guideline published by the American Thoracic Society, European Respiratory Society,
Japanese Respiratory Society, and Latin American Thoracic Society coined the term
"progressive pulmonary fibrosis" (PPF) and laid out diagnostic criteria for this phenotype
[39]. These criteria are as follows:
● Presence of ILD other than IPF with radiologic evidence of lung fibrosis
● Two of the following three signs of fibrotic disease progression within the past year
without alternative explanation:
• 1) Worsening restrictive physiology (absolute decline in forced vital capacity [FVC] ≥5

percent predicted or absolute decline in diffusing capacity for carbon monoxide
[DLCO] ≥10 percent predicted),
• 2) Worsening respiratory symptoms, or
• 3) Progression of radiologic fibrosis (increased extent or severity of reticular

changes, lobar volume loss, or traction bronchiectasis/bronchiolectasis, new
ground-glass opacities with traction bronchiectasis, or new/worsening
honeycombing)
Notably, these criteria were not based on clear data, and will likely require additional
refinement over time. Like many experts in the field, we believe that progression should be
judged independent of timeline (ie, progression should be established based on clinical,
physiologic, or radiographic evidence regardless of the timeframe over which the change
occurred) [46,47]. It is also unlikely that all patients meeting PPF criteria have similar risks of
poor outcomes regardless of their underlying disease or which criteria they meet. For
example, one study of several cohorts showed that for most criteria, rate of lung function
decline after demonstrating progressive fibrosis was much lower for patients with ILD
associated with connective tissue disease than for those with chronic hypersensitivity
pneumonitis or a non-IPF idiopathic interstitial pneumonia [48]. Similarly, while some
criteria, such as relative FVC decline ≥10 percent, appear to identify cohorts of patients with
prognosis similar to that of patients with IPF, other criteria were not consistent across
cohorts or disease subtypes [41].
While awaiting further refinements, we use the 2022 PPF criteria above as evidence of
worsening fibrosis in patients with known fibrotic ILDs, including connective tissue disease-
associated ILDs, chronic hypersensitivity pneumonitis, and idiopathic interstitial pneumonias
(other than IPF).
● Nintedanib – For patients with non-IPF ILD who develop PPF despite optimal initial ILD
management (eg, antigen avoidance or immunosuppressive treatment, depending on
ILD subtype), we suggest treatment with nintedanib to reduce the rate of lung function
decline. The primary evidence for this approach is based on a placebo-controlled trial
that enrolled 663 patients with fibrotic ILD and either a ≥10 percent relative decline in
FVC or more than a 5 percent relative decline in FVC accompanied by worsening
respiratory symptoms or fibrotic changes over the past 24 months [43]. Treatment with
nintedanib (150 mg orally twice daily) resulted in a reduced adjusted decline in FVC at
52 weeks (-80.8 ml with nintedanib and -187.8 ml with placebo; difference +107 mL,
95% CI 65.4 to 148.5). The effect on FVC decline was similar in patients that had a usual
interstitial pneumonia pattern (-82.9 ml with nintedanib and -211.1 ml with placebo;
difference +128 mL, 95% CI 70.8 to 185.6). There were no clinically significant changes
in ILD symptom scores. Diarrhea occurred more commonly with nintedanib treatment
compared with placebo (66.9 percent versus 23.9 percent) and led to dose reduction or
discontinuation of nintedanib in 33 and 20 percent of patients, respectively.
● Pirfenidone – Two trials have examined pirfenidone in patients with progression of

fibrotic ILD. In one placebo-controlled trial of 253 patients with worsening unclassifiable
fibrotic ILD, patients receiving pirfenidone (2403 mg orally daily) demonstrated reduced
decline in FVC over 24 weeks (-18 versus -113 mL, difference +95 mL, 95% CI 36 to 155
mL) [45]. There were no meaningful differences in patient-reported outcomes or six-
minute walk distance. A second trial that included patients with specific ILD diagnoses
was stopped early for poor recruitment and required statistically modeling due to
missing data; some models suggested a similar effect size to that seen in the other trial
[44]. Based on these limited data, we only offer pirfenidone (off-label) to patients with
PPF who are unable to take nintedanib. Availability and insurance coverage may be
barriers to pirfenidone use.
For patients initiated on antifibrotic therapy for PPF, the continuation of prior anti-
inflammatory therapies should be tailored to the individual patient and the underlying cause
of ILD. In general, for patients who have progressed despite standard of care (including
immunosuppression), we attempt add-on antifibrotic therapy. Depending on patient
tolerance, anti-inflammatory therapy may be maintained, dose-reduced, or discontinued. For
those with connective tissue disease-associated ILD, anti-inflammatory agents are commonly
needed to control extrapulmonary manifestations of their disease. Additional observational
and clinical trial data are needed to help inform best practices regarding concomitant
antifibrotic and anti-inflammatory therapy. (See "Interstitial lung disease in rheumatoid
arthritis", section on 'Antifibrotic therapy, for progressive fibrosis' and "Treatment and
prognosis of interstitial lung disease in systemic sclerosis (scleroderma)", section on
'Progressive disease' and "Treatment and prognosis of nonspecific interstitial pneumonia",
section on 'Nintedanib'.)
Because progressive fibrotic changes are rarely reversible, patients with PPF should also be
re-evaluated for optimal general care measures, including oxygen, pulmonary rehabilitation,
and palliative therapies for refractory symptoms. (See 'General care measures for patients
with ILD' above.)
Patients with new ground-glass changes — The differential diagnosis of new ground-glass
opacities on CT includes respiratory infection, acute decompensated heart failure, aspiration,
and acute exacerbation of the underlying ILD. Differentiating between these entities confers
both prognostic and therapeutic implications.
● Respiratory infection – Evaluation for respiratory infection commonly includes sputum

sampling and respiratory viral panels. In cases where the ILD patient is receiving
systemic glucocorticoids or other immunosuppressive therapies, atypical infections,
such as pneumocystis jirovecii pneumonia, aspergillosis, and endemic fungal
pneumonia, should also be considered. In certain cases, particularly in the absence of
sputum production, bronchoscopy with bronchoalveolar lavage may be necessary for
further evaluation. (See "Epidemiology of pulmonary infections in
immunocompromised patients" and "Approach to the immunocompromised patient
with fever and pulmonary infiltrates".)
● Decompensated heart failure – Weight gain, orthopnea, vascular distribution of

ground-glass opacities, presence of pleural effusions, and lower extremity edema
suggest acute decompensated heart failure. Obtaining a brain natriuretic peptide or N-
terminal probrain natriuretic peptide level can be helpful in determining volume status.
If cardiac dysfunction is new, an electrocardiogram and echocardiography should be
obtained. The mainstay of treatment for pulmonary symptoms is typically initiating or
increasing diuretic therapy. The diagnosis and management of heart failure are
discussed separately. (See "Approach to diagnosis and evaluation of acute
decompensated heart failure in adults" and "Treatment of acute decompensated heart
failure: General considerations".)
● Aspiration – Acute or recurrent aspiration are common causes of worsening

pulmonary inflammation. In addition to historical evidence of aspiration (eg, choking
episodes, vomiting, taste of bile in the throat), CT imaging demonstrating lower lobe
predominance of ground-glass opacities and/or consolidation (particularly on the right
side), airway-centric inflammatory changes, tree-in-bud opacities, or a patulous
esophagus are suggestive of possible aspiration. Aspiration pneumonitis in the setting
of ILD may spontaneously resolve, evolve into an aspiration pneumonia, or result in an
acute exacerbation of ILD (AE-ILD; see below). From a management standpoint, further
evaluation and prevention of recurrent aspiration may help prevent recurrent episodes.
We typically obtain a swallowing evaluation and/or esophageal imaging and
manometry for further evaluation, depending on the patient's symptoms. (See
"Approach to the evaluation of dysphagia in adults".)
● Iatrogenic lung toxicity – Patients with ILD are more symptomatic and likely more
susceptible to drug-induced or radiation-induced lung injury. Diffuse ground-glass
changes in temporal association with high-risk agents (eg, bleomycin, nitrofurantoin, or
immune checkpoint inhibitors ( table 8)) should prompt discontinuation of the
potentially inciting drug pending further work-up. If no other cause is found, we

generally avoid resuming the offending agent. In the case of radiation-induced lung
injury, the inflammation is frequently present in the radiation field, but radiation injury
can also lead to an acute exacerbation of fibrotic ILD (below) that demonstrates a more
diffuse injury pattern. The inflammation generally occurs 3 to 12 weeks after injury.
Most symptomatic drug-induced or radiation-induced lung injury is treated with a
course of moderate-dose systemic glucocorticoids tapered over several weeks based on
patient response. (See "Radiation-induced lung injury" and "Pulmonary toxicity
associated with systemic antineoplastic therapy: Clinical presentation, diagnosis, and
treatment" and "Pulmonary toxicity associated with antineoplastic therapy: Molecularly
targeted agents" and "Nitrofurantoin-induced pulmonary injury".)
● Acute exacerbation of ILD (AE-ILD) – While acute exacerbations are well-described in

IPF, acute exacerbations can also occur in other ILDs associated with lung fibrosis,
including other idiopathic interstitial pneumonias, chronic hypersensitivity
pneumonitis, and connective tissue disease-associated ILDs [49-51]. The key diagnostic
feature of an acute exacerbation is the presence of new bilateral ground-glass opacities
or consolidation (on a background of underlying pulmonary fibrosis) that occurs over a
subacute time frame (<1 month duration) and is not fully explained by heart failure [27].
Other causes of lung injury (eg, infection, aspiration, and iatrogenic injury [above]) may
"trigger" an acute exacerbation in susceptible patients; for some patients, no trigger
can be identified. There are minimal prospective data to guide treatment of patients
with AE-ILD. We suggest attempted treatment with systemic glucocorticoids (1 mg/kg
up to 1,000 mg of methylprednisolone [or equivalent], depending on severity of the
exacerbation) and use concomitant antibiotic therapy empirically or pending an
infectious work-up. Glucocorticoids are tapered slowly based on response in those who
improve; we typically do not continue them in patients who do not respond to high
doses over the first three to five days. Acute exacerbations portend a very poor
prognosis in those with IPF; limited data suggest a substantial short-term mortality, but
slightly better prognosis, in patients with AE-ILD from other fibrotic lung diseases [49].
(See "Acute exacerbations of idiopathic pulmonary fibrosis" and "Acute interstitial
pneumonia (Hamman-Rich syndrome)".)
As an exception to this approach, cyclophosphamide, rather than high-dose

glucocorticoids, may be used for AE-ILD associated with scleroderma to avoid the risk
of precipitating scleroderma renal crisis. (See "Kidney disease in systemic sclerosis
(scleroderma), including scleroderma renal crisis", section on 'Prevention'.)
Patients with fulminant or rapidly progressive ILD associated with dermatomyositis or

polymyositis (typically those with melanoma differentiation-associated gene 5 [MDA5]
antibodies) have diseases that mimic AE-ILD, but they are typically treated both with
high-dose glucocorticoids and concomitant additional immunosuppressants, including

cyclophosphamide. (See "Interstitial lung disease in dermatomyositis and polymyositis:
Treatment", section on 'ILD associated with MDA5 antibody'.)
Patients with other ILDs, such as sarcoidosis, hypersensitivity pneumonitis, or

cryptogenic organizing pneumonia, may present with new ground-glass inflammatory
changes due to increased underlying disease activity in the absence of underlying
fibrosis. These episodes are usually called "flares" or "relapses," rather than acute
exacerbations. They are most commonly associated with tapering or cessation of anti-
inflammatory therapies or (in the case of hypersensitivity pneumonitis) new or
worsening antigen exposure. Anti-inflammatory therapies are typically very effective in
this setting, and significantly lower doses (eg, ≤60 mg of prednisone orally daily) are
typically used. (See "Treatment of pulmonary sarcoidosis: Initial approach", section on
'Relapses and acute bronchitic symptoms' and "Cryptogenic organizing pneumonia",
section on 'Treatment of relapses during glucocorticoid taper' and "Hypersensitivity
pneumonitis (extrinsic allergic alveolitis): Treatment, prognosis, and prevention",
section on 'Acute or subacute HP with persistent symptoms'.)
In those with severe AE-ILD requiring hospitalization, shared decision-making around

end-of-life care is of critical importance. Although frequently offered, invasive
mechanical ventilation is typically of limited utility in this setting. For example, in one
study of 94 patients with AE-ILD, only 5 percent of those with IPF and 14 percent of
those with connective tissue disease-associated ILD survived their index hospitalization
following invasive mechanical ventilation [52]. Rarely, in patients who have already
been listed for transplantation and are hospitalized at a transplant center, a time-
limited trial of mechanical ventilation or extracorporeal membrane oxygenation can be
used as a bridge to transplant [53].
Worsening air-trapping or obstruction — Patients with ILD can develop worsening

obstruction and air-trapping due to comorbid asthma or chronic obstruction pulmonary
disease (COPD), development of obstructive bronchiolitis (in patients with certain connective
tissue diseases), or due to progression of airway pathology associated with ILD (eg,
hypersensitivity pneumonitis or sarcoidosis). It is important to differentiate worsening
obstruction from progressive restrictive changes, as treatment may be different depending
on the underlying cause. (See "Overview of bronchiolar disorders in adults" and "Treatment
of pulmonary sarcoidosis: Initial approach", section on 'Relapses and acute bronchitic
symptoms'.)
Isolated worsening diffusing capacity — An isolated worsening diffusing capacity or a

diffusing capacity that worsens out of proportion to a decline in FVC should prompt
evaluation for PH via transthoracic echocardiogram and, in some cases, right heart
catheterization.
Patients with advanced ILD are at increased risk of developing PH associated with alveolar
destruction and hypoxemia (group three PH). Certain systemic diseases associated with ILD
also increase the risk for PH even in the absence of advanced interstitial disease; these
include sarcoidosis, scleroderma, mixed connective tissue disease, and rheumatoid arthritis.
(See "Pulmonary hypertension due to lung disease and/or hypoxemia (group 3 pulmonary
hypertension): Epidemiology, pathogenesis, and diagnostic evaluation in adults" and
"Sarcoidosis-associated pulmonary hypertension: Diagnostic evaluation in adults" and
"Pulmonary arterial hypertension in systemic sclerosis (scleroderma): Treatment and
prognosis" and "Overview of pleuropulmonary diseases associated with rheumatoid
arthritis", section on 'Pulmonary hypertension'.)
Because both PH and ILD cause dyspnea and hypoxemia, it can be difficult to differentiate
worsening ILD versus the development of PH based on symptoms or clinical examination
alone; isolated changes in DLCO or changes in DLCO out of proportion to changes in vital
capacity increase suspicion for PH. Acute decompensated heart failure can also negatively
impact DLCO due to poor cardiac output and pulmonary edema, but can often be
determined clinically or by imaging (above). Chronic heart failure may itself contribute to the
development of PH. Anemia is also a common cause of isolated reduced diffusing capacity.
The pulmonary function test (PFT) laboratory will typically obtain a hemoglobin and report a
corrected value, but patients without corrected values should be tested for anemia prior to
additional evaluation. (See "Diffusing capacity for carbon monoxide", section on
'Adjustments'.)
After transthoracic echocardiogram evaluation, patients at moderate or high suspicion for

PH often require cardiac catheterization for diagnosis and categorization. Postdiagnostic
testing may include further work-up for additional potential contributory causes, including
sleep apnea, chronic thromboembolic disease, and connective tissue diseases, particularly
when the PH is more severe than expected for the extent of ILD. (See "Clinical features and
diagnosis of pulmonary hypertension of unclear etiology in adults".)
No change in PFTs or chest imaging — Common causes of worsening pulmonary

symptoms without changes in imaging or pulmonary function include pulmonary embolism,
cardiac disease, thyroid dysfunction, medication side effects, and deconditioning.
● Venous thromboembolism – There is some evidence to suggest that patients with ILD
are at increased risk for developing venous thromboembolism [54]. Whether this risk is
limited to certain types of ILD (such as IPF) or affects all patients with ILD is not well
understood. Patients with advanced ILD may be at increased risk due to limited
mobility arising from symptom severity and hypoxemia. Worsening tachypnea,
tachycardia, and breathlessness, especially those of acute onset, without changes on

chest radiograph, noncontrast CT, or PFTs should prompt evaluation for venous
thromboembolism. (See "Clinical presentation, evaluation, and diagnosis of the
nonpregnant adult with suspected acute pulmonary embolism".)
● Coronary artery disease – Coronary artery disease is a common comorbidity in

patients with ILD, especially those of advanced age [55]. Progressive dyspnea, primarily
with exertion, in a patient with risk factors should prompt evaluation for possible
coronary ischemia. Paroxysmal episodes of dyspnea and palpitations may also arise
from supraventricular tachycardias, which are more common in patients with advanced
lung disease [56]. Clinical evaluation, including electrocardiogram and referral to a
cardiologist, may be appropriate. (See "Approach to the patient with suspected angina
pectoris" and "Narrow QRS complex tachycardias: Clinical manifestations, diagnosis,
and evaluation".)
● Fatigue – Fatigue, dyspnea, and exhaustion have overlapping features that are difficult
for patients to differentiate. Worsening dyspnea in the absence of change in imaging or
PFTs frequently arises from fatigue or deconditioning rather than from a pulmonary
etiology. When evaluating possible fatigue, we consider assessment of thyroid function,
changes in medications (fatigue is a frequent side effect of many pharmaceuticals), and
underlying disease. Fatigue is a major, difficult-to-treat feature of sarcoidosis and many
connective tissue diseases; fatigue severity in these conditions is typically not related to
the severity of the ILD. Deconditioning is also very common in patients with ILD and is
to be expected after acute illnesses or other reasons for relative immobility.
Deconditioning in the setting of ILD may improve with pulmonary rehabilitation. (See
'Pulmonary rehabilitation' above.)
● Occult disease progression – As a diagnosis of exclusion, some individuals may

experience worsening pulmonary symptoms from ILD progression prior to changes in
imaging or PFTs. For those whom another cause is not found or highly uncertain, we
typically monitor more closely over the next several months for objective evidence of
worsening ILD. (See 'Ongoing monitoring of patients with ILD' above.)
REFERRAL FOR LUNG TRANSPLANTATION EVALUATION
Patients with advanced ILD without other contraindications should undergo evaluation for
and counseling about lung transplantation at a lung transplant center. For those with fibrotic
ILDs, the poor prognosis after progression and risk of decompensation in the setting of
acute exacerbation merits early referral. Our practice is consistent with the International
Society of Heart and Lung Transplantation guidelines, which suggest relatively early referral
for these patients, with listing of appropriate candidates after evidence of disease
progression [57]. (See "Lung transplantation: An overview" and "Lung transplantation:

Disease-based choice of procedure".)
Most patients with fibrotic-appearing features of ILD on imaging or pathology are

appropriate for initial referral to a transplant center to begin evaluation and counseling.
Exceptions include:
● Patients who have evident disease but no symptoms and minimal lung function
abnormalities. We often defer transplant evaluation until there is some progression of
disease.
● Patients with treatment plans that include anti-inflammatory therapy. In these patients,
we usually defer referral or listing until we can assess response to initial anti-
inflammatory treatments, unless their disease presentation is rapid or severe. Patients
with disease progression despite anti-inflammatory therapy and without other
contraindications are appropriate for lung transplant referral.
For patients with ILD referred to transplant for any of the above indications, criteria for
placing appropriate candidates on the transplant list include the following [57]:
● Decline in FVC ≥10 percent predicted during six months of follow-up (a decline ≥5
percent predicted with radiographic progression also warrants listing)
● Decline in DLCO ≥10 percent predicted during six months of follow-up
● On six-minute walk test: oxygen desaturation to <88 percent, distance walked <250
meters, or >50 meter decline in distance walked over six months
● Pulmonary hypertension (PH) on right heart catheterization or transthoracic

echocardiogram
● Hospitalization because of respiratory decline, pneumothorax, or acute exacerbation
REFERRAL FOR END-OF-LIFE CARE
In the absence of lung transplantation, advanced progressive ILDs have a terminal

prognosis. Where available, hospice care is appropriate for patients with end-stage
pulmonary disease with life expectancy of six months or less. Hospice criteria for end-stage
pulmonary disease include [58]:
● Disabling dyspnea at rest, poorly responsive or unresponsive to bronchodilators,

resulting in decreased functional capacity (eg, bed to chair existence, fatigue, and
cough)
● Progression of end-stage pulmonary disease, as evidenced by increasing visits to the

emergency department or hospitalizations for pulmonary infections and/or respiratory
failure
● Hypoxemia (as evidenced by pO2 ≤55 mmHg, or oxygen saturation ≤88 percent) or
hypercapnia (as evidenced by pCO2 ≥50 mmHg) at rest on room air
Other common features of end-stage ILD include worsening pulmonary hypertension (PH)
and cor pulmonale, unintentional progressive weight loss (especially greater than 10
percent), and resting tachycardia.
Additional information regarding palliative care at the end of life and hospice care is
discussed elsewhere. (See "Palliative care for adults with nonmalignant chronic lung disease"
and "Hospice: Philosophy of care and appropriate utilization in the United States" and
"Palliative care and hospice outside of the United States".)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Interstitial lung
disease" and "Society guideline links: Sarcoidosis" and "Society guideline links: Palliative care"
and "Society guideline links: Pulmonary rehabilitation" and "Society guideline links:
Supplemental oxygen".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, “The Basics” and “Beyond the
Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have
about a given condition. These articles are best for patients who want a general overview
and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are
longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th
grade reading level and are best for patients who want in-depth information and are
comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
● Basics topics (See "Patient education: Interstitial lung disease (The Basics)" and "Patient
education: Idiopathic pulmonary fibrosis (The Basics)" and "Patient education:
Sarcoidosis (The Basics)" and "Patient education: Pulmonary rehabilitation (The

Basics)".)
SUMMARY AND RECOMMENDATIONS
● Routine monitoring – Clinical follow-up of patients with interstitial lung disease (ILD)
involves reassessment of pulmonary symptoms, evaluation of extrapulmonary
manifestations of disease, assessment of common comorbidities, and managing
complications and toxicities of pharmacologic treatments. We typically perform
surveillance of pulmonary function using spirometry and diffusing capacity at regular
intervals depending on disease stability and changes in symptoms. (See 'Ongoing
monitoring of patients with ILD' above.)
● General care measures – For all patients with ILD, we encourage tobacco cessation
and support group participation. We also evaluate the need for oxygen therapy,
pulmonary rehabilitation, nutritional support, and palliative treatments of refractory
cough and dyspnea. (See 'General care measures for patients with ILD' above.)
To prevent pulmonary infection and lung injury, our typical practice also includes:
• Vaccination against respiratory infections, including streptococcus pneumoniae,

influenza, Bordetella pertussis, SARS-CoV-2, and respiratory syncytial virus (for those
over age 60)
• Evaluation and treatment of symptomatic gastroesophageal reflux and

oropharyngeal dysphagia
• Avoidance of mechanical ventilation or general anesthesia when possible, and

otherwise use of lung-protective ventilation strategies
● Treatment principles – The pharmacologic treatment of ILD varies based on diagnosis,

predominant imaging pattern, and pathologic features. Diseases associated with
environmental or drug exposures (including smoking) benefit most from avoidance of
the antigen, toxin, or exposure. Multidisciplinary discussion of clinical factors, imaging,
and pathology (when available) can help guide management strategy towards anti-
inflammatory, antifibrotic, or combination therapies. (See 'General treatment principles'
above.)
● Approach to the patient with worsening symptoms – For patients with worsening
pulmonary symptoms, initial diagnostic steps usually include pulmonary function
testing and imaging such as a chest radiograph or CT, tailored based on the presenting
symptoms. Additional evaluation and treatment are based on the results of this initial
work-up. (See 'General approach and differential diagnosis' above.)
• Progressive fibrotic changes and/or worsening restriction – The development of

progressive fibrosis and worsening restriction is expected in the patient with
idiopathic pulmonary fibrosis (IPF), and may lead to initiation or adjustment in
treatment (see "Treatment of idiopathic pulmonary fibrosis", section on 'Medical
therapies'). For patients with non-IPF fibrotic ILDs, progressive pulmonary fibrosis is
currently defined by two of the following three characteristics: worsening restrictive
physiology, increased respiratory symptoms, and progression of radiologic fibrosis.
These criteria likely need further refinement, and patients within this group do not
have homogeneous risk of further progression. (See 'Patients with progressive
fibrotic changes or worsening restriction' above.)
For patients with non-IPF ILD who develop progressive pulmonary fibrosis despite
optimal initial ILD management, we suggest treatment with nintedanib (Grade 2C)
based on data demonstrating reductions in the rate of lung function decline. For
patients with progressive pulmonary fibrosis who cannot use nintedanib, off-label
treatment with pirfenidone is a reasonable alternative.
• New ground-glass changes – The differential diagnosis of new ground-glass

opacities on computed tomography includes respiratory infection, acute
decompensated heart failure, aspiration, and acute exacerbation of the underlying
ILD.
For patients without IPF and a suspected acute exacerbation of ILD, we suggest a
trial of systemic glucocorticoids rather than supportive care (Grade 2C), although
there are minimal prospective data to guide treatment. We typically use 1 mg/kg up
to 1,000 mg of methylprednisolone daily or the equivalent, depending on the
severity of the exacerbation. Glucocorticoids are tapered slowly over days to weeks
based on response in those who improve; we typically do not continue them in
patients who do not respond to high doses over the first three to five days. (See
'Patients with new ground-glass changes' above.)
Treatment of acute exacerbations of IPF is discussed separately. (See "Acute

exacerbations of idiopathic pulmonary fibrosis", section on 'Treatment'.)
• Isolated worsening diffusing capacity – Symptomatic ILD accompanied by an

isolated worsening diffusing capacity or a diffusing capacity that worsens out of
proportion to a decline in forced vital capacity (FVC) should prompt evaluation for
pulmonary hypertension (PH) via transthoracic echocardiogram. (See 'Isolated
worsening diffusing capacity' above.)
• No change in pulmonary function tests (PFTs) or imaging – Common causes of

worsening pulmonary symptoms without changes in imaging or pulmonary function
include pulmonary embolism, cardiac disease, thyroid dysfunction, medication side
effects, and deconditioning.
● Referral for lung transplant evaluation – Patients with advanced ILD without other
contraindications should undergo evaluation for and counseling about lung
transplantation at a lung transplant center. For those with fibrotic ILDs, the poor
prognosis after progression and risk of decompensation in the setting of acute
exacerbation merits early referral. (See 'Referral for lung transplantation evaluation'
above.)
● Referral for end-of-life care – Patients with disabling dyspnea or functional capacity at
rest, escalating hospitalizations, severe hypoxemia, cor pulmonale due to ILD, or
unintentional progressive weight loss are appropriate for end-of-life palliative
interventions, including hospice referral. (See 'Referral for end-of-life care' above.)
Use of UpToDate is subject to the Terms of Use.
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blind, randomised, placebo-controlled, phase 2b trial. Lancet Respir Med 2021; 9:476.
45. Maher TM, Corte TJ, Fischer A, et al. Pirfenidone in patients with unclassifiable
progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-
controlled, phase 2 trial. Lancet Respir Med 2020; 8:147.
46. Cottin V, Brown KK, Flaherty KR, Wells AU. Progressive Pulmonary Fibrosis: Should the
Timelines Be Taken Out of the Definition? Am J Respir Crit Care Med 2022; 206:1293.
47. Vu Pugashetti J, Newton CA, Molyneaux PL, Oldham JM. Reply to Noboa-Sevilla et al. Am J
Respir Crit Care Med 2023; 207:369.
48. Oldham JM, Lee CT, Wu Z, et al. Lung function trajectory in progressive fibrosing
interstitial lung disease. Eur Respir J 2022; 59.
49. Okuda R, Takemura T, Misumi T, et al. Acute Exacerbation and Proposed Criteria for
Progressive Pulmonary Fibrosis in Patients with Fibrotic Hypersensitivity Pneumonitis
and Idiopathic Pulmonary Fibrosis. Respiration 2023; 102:803.
50. Enomoto N, Naoi H, Mochizuka Y, et al. Frequency, proportion of PF-ILD, and prognostic
factors in patients with acute exacerbation of ILD related to systemic autoimmune
diseases. BMC Pulm Med 2022; 22:387.
51. Kwon BS, Lee HY, Choe J, et al. Acute Respiratory Deterioration in Rheumatoid Arthritis-
Associated Interstitial Lung Disease: A Single-Center Study. Chest 2022; 162:136.
52. Luo Z, Yang L, Liu S, et al. Mechanical ventilation for acute respiratory failure due to
idiopathic pulmonary fibrosis versus connective tissue disease-associated interstitial
lung disease: Effectiveness and risk factors for death. Clin Respir J 2020; 14:918.
53. Dotan Y, Vaidy A, Shapiro WB, et al. Effect of Acute Exacerbation of Idiopathic Pulmonary
Fibrosis on Lung Transplantation Outcome. Chest 2018; 154:818.
54. Dalleywater W, Powell HA, Fogarty AW, et al. Venous thromboembolism in people with
idiopathic pulmonary fibrosis: a population-based study. Eur Respir J 2014; 44:1714.
55. Kizer JR, Zisman DA, Blumenthal NP, et al. Association between pulmonary fibrosis and
coronary artery disease. Arch Intern Med 2004; 164:551.
56. Carter P, Lagan J, Fortune C, et al. Association of Cardiovascular Disease With Respiratory
Disease. J Am Coll Cardiol 2019; 73:2166.
57. Leard LE, Holm AM, Valapour M, et al. Consensus document for the selection of lung
transplant candidates: An update from the International Society for Heart and Lung
Transplantation. J Heart Lung Transplant 2021; 40:1349.
58. Centers for Medicare & Medicaid Services. Medicare Coverage Database. Local Coverage
Determination (LCD): Hospice Determining Terminal Status (L34538). Available at: http
s://www.cms.gov/medicare-coverage-database/details/lcd-details.aspx?LCDId=34538 (Ac
cessed on June 01, 2021).
Topic 140067 Version 1.0
GRAPHICS
Diffuse parenchymal lung diseases
Diffuse parenchymal lung diseases consist of disorders of known causes (rheumatic disease,
environmental or drug related) as well as disorders of unknown cause. The latter include IIPs,
granulomatous lung disorders (eg, sarcoidosis), and other forms of interstitial lung disease including
LAM, PLCH, and eosinophilic pneumonia. The interstitial pneumonias are further categorized as
chronic fibrosing, acute or subacute fibrosing, or smoking-related. Lymphoid interstitial pneumonia is
typically associated with other disease processes, such as rheumatic disease or immunosuppression;
idiopathic lymphoid interstitial pneumonia is rare.
DPLD: diffuse parenchymal lung disease; IIP: idiopathic interstitial pneumonia; LAM:
lymphangioleiomyomatosis; PLCH: pulmonary Langerhans cell histiocytosis/histiocytosis X.
Graphic 77345 Version 11.0
Extrapulmonary findings in the interstitial lung diseases
Physical findings Associated conditions
Systemic arterial hypertension
Systemic rheumatic disease, neurofibromatosis,

anti-GBM antibody syndrome, systemic vasculitis
Skin
Discoid lupus IPF, SLE, drug-induced SLE
Maculopapular rash Drug-induced, amyloidosis, systemic rheumatic

disease, Gaucher's disease
Heliotrope rash; Gottron papules; poikiloderma Dermatomyositis
Mechanic's hands Antisynthetase syndrome
Palmar papules, ulcerating lesions Amyopathic dermatomyositis
Telangiectasia, sclerodactyly, Systemic sclerosis (scleroderma)

hyperpigmentation/hypopigmentation, digital
ulcers or pitting
Raynaud phenomenon Systemic rheumatic disease (scleroderma, SLE,

mixed systemic rheumatic disease)
Cafe-au-lait spots, neurofibromas Neurofibromatosis
Cutaneous vasculitis (eg, palpable purpura) Systemic vasculitides; systemic rheumatic disease
Reticulated or mottled skin hyperpigmentation, Dyskeratosis congenita

nail dystropy, mucosal leukoplakia
Albinism Hermansky-Pudlak syndrome
Calcinosis Dermatomyositis-polymyositis; scleroderma
Subcutaneous nodules Rheumatoid arthritis, neurofibromatosis, ANCA-

associated vasculitis
Erythema nodosum (deep, painful nodules Sarcoidosis; systemic rheumatic disease; Behçet
predominantly on anterior surfaces lower syndrome; inflammatory bowel disease;
extremities) histoplasmosis, coccidioidomycosis
Eyes
Uveitis Sarcoidosis (eg, mutton-fat keratic precipitates),

Behçet syndrome (eg, panuveitis, hypopyon),
ankylosing spondylitis (eg, acute anterior uveitis)
Scleritis ANCA-associated vasculitis, SLE, systemic sclerosis

(scleroderma), sarcoidosis
Keratoconjunctivitis sicca Lymphocytic interstitial pneumonia (in Sjögren

syndrome)
Cherry red macula, macular halo Neiman-Pick disease
Hematologic and reticuloendothelial system
Peripheral lymphadenopathy Sarcoidosis, lymphangitic carcinomatosis,

lymphocytic interstitial pneumonia, lymphoma,
LAM-TSC
Hepatosplenomegaly Sarcoidosis, pulmonary Langerhans cell

histiocytosis, systemic rheumatic disease,
amyloidosis, lymphocytic interstitial pneumonia
Anemia, thrombocytopenia, hypocellular Dyskeratosis congenita

marrow
Heart
Pericarditis, pericardial effusion Radiation pneumonitis, systemic rheumatic

disease, LAM-TSC
Cardiomyopathy ANCA-associated vasculitis, sarcoidosis, SLE
Musculoskeletal/neurologic
Muscle weakness Systemic rheumatic disease, drugs (eg, statins),

sarcoidosis
Nervous system abnormalities Pulmonary Langerhans cell histiocytosis, Neiman-

Pick disease, neurofibromatosis, sarcoidosis, SLE,
systemic vasculitis, TSC
Arthritis ANCA-associated vasculitis, Rheumatoid arthritis,

SLE, sarcoidosis (predominantly periarthritis of
ankles and knees)
Gastrointestinal/renal
Glomerulonephritis Anti-GBM antibody syndrome, ANCA-associated

vasculitis, sarcoidosis
Nephrotic syndrome Amyloid, drug-induced, sarcoidosis, SLE
Renal mass (eg, angiomyolipoma) TSC, LAM
Gastrointestinal symptoms (eg, diarrhea, Pneumonitis related to inflammatory bowel

abdominal pain, hematochezia) disease
Other
Salivary or lacrimal gland enlargement Sarcoidosis, lymphocytic interstitial pneumonia (in

Sjögren syndrome), IgG4-related disease
Pleural abnormalities Systemic rheumatic disease, LAM-TSC (chylous

effusion), abestosis
GBM: glomerular basement membrane; IPF: idiopathic pulmonary fibrosis; SLE: systemic lupus
erythematosus; ANCA: antineutrophil cytoplasmic antibodies; LAM: lymphangioleiomyomatosis; TSC:
tuberous sclerosis complex; IgG4: immunoglobulin G4.
Adapted from:
1. Schwarz MI, King TE Jr, Cherniack RM. General principles and diagnostic approach to the interstitial lung diseases. In:
Murray JF, Nadel JA, (Eds), Textbook of Respiratory Medicine, 2nd ed, Philadelphia, WB Saunders Co, 1994, pp. 1803-
1826.
2. Cosgrove GP, Schwarz MI. Approach to the evaluation and diagnosis of interstitial lung diseases. In: Interstitial Lung
Disease, 5th ed, Shelton, CT, Peoples Medical Publishing House, 2011, pp. 3-33.
Major adverse effects associated with systemic glucocorticoid therapy *
Metabolic and endocrine
Hypothalamic-pituitary-adrenal axis suppression
Hyperglycemia
Dermatologic and appearance

Cushingoid features
Weight gain
Skin thinning and ecchymoses
Acne, hirsutism, facial erythema
Cardiovascular
Fluid retention
Hypertension
Premature atherosclerotic disease and major cardiac events (eg, myocardial infarction, stroke)
Arrhythmias
Pulmonary emboli and venous thromboembolism
Possible hyperlipidemia
Gastrointestinal
Gastritis, peptic ulcer disease, and upper gastrointestinal bleeding
Steatohepatitis
Visceral perforation
Bone and muscle effects

Osteoporosis
Osteonecrosis/avascular necrosis
Myopathy
Neuropsychiatric
Insomnia
Depression
Psychosis
Memory impairment
Ophthalmologic
Cataracts
Elevated intraocular pressure/glaucoma
Immune system
Increased risk of infections
Decreased response to vaccinations
Other
Tooth hypersensitivity
Epistaxis
Growth impairment in children
Adverse effects may vary depending on other patient risk factors and the anticipated dose and
duration of glucocorticoids. Refer to UpToDate for additional details.
* High-dose inhaled glucocorticoid therapy can rarely cause systemic adverse effects. Refer to
UpToDate content for information on local adverse effects of inhaled glucocorticoids.
Adult immunization schedule by age - Recommendations for ages 19 years o

older, United States, 2024
Administer recommended vaccines if vaccination history is incomplete or unknown. Do not restart or

add doses to vaccine series if there are extended intervals between doses. The use of trade names is
for identification purposes only and does not imply endorsement by the ACIP or CDC.
NOTES
For vaccine recommendations for persons 18 years of age or younger, refer to the Recommended
Child and Adolescent Immunization Schedule.
Additional information
For calculating intervals between doses, 4 weeks = 28 Intervals of ≥4 months are determined by
calendar months.
Within a number range (eg, 12-18), a dash (–) should be read as "through."
Vaccine doses administered ≤4 days before the minimum age or interval are considered valid.
Doses of any vaccine administered ≥5 days earlier than the minimum age or minimum interval
should not be counted as valid and should be repeated. The repeat dose should be spaced
after the invalid dose by the recommended minimum interval. For further details, refer to
Table 3-2, Recommended and minimum ages and intervals between vaccine doses, in General
Best Practice Guidelines for Immunization.
Information on travel vaccination requirements and recommendations is available at
cdc.gov/travel/.
For vaccination of persons with immunodeficiencies, refer to Table 8-1, Vaccination of persons
with primary and secondary immunodeficiencies, in General Best Practice Guidelines for
Immunization.
For information about vaccination in the setting of a vaccine-preventable disease outbreak,
contact your state or local health department.
The National Vaccine Injury Compensation Program (VICP) is a no-fault alternative to the
traditional legal system for resolving vaccine injury claims. All vaccines included in the adult
immunization schedule except PPSV23, RSV, RZV, Mpox, and COVID-19 vaccines are covered by
the National Vaccine Injury Compensation Program (VICP). Mpox and COVID-19 vaccines are
covered by the Countermeasures Injury Compensation Program (CICP). For more information,
refer to www.hrsa.gov/vaccinecompensation or www.hrsa.gov/cicp.
Polio vaccination
Routine vaccination:
Adults known or suspected to be unvaccinated or incompletely vaccinated: Administer
remaining doses (1, 2, or 3 IPV doses) to complete a 3-dose primary series (NOTE: Complete
primary series consists of at least 3 doses of IPV or trivalent oral poliovirus vaccine [tOPV] in
any combination). Unless there are specific reasons to believe they were not vaccinated, most
adults who were born and raised in the United States can assume they were vaccinated
against polio as children.
Special situations:
Adults at increased risk of exposure to poliovirus who completed primary series (NOTE:
Complete primary series consists of at least 3 doses of IPV or trivalent oral poliovirus vaccine
[tOPV] in any combination): May administer one lifetime IPV booster.
For detailed information, refer to
www.cdc.gov/vaccines/vpd/polio/hcp/recommendations.html.
Contraindications and precautions:
For contraindications and precautions to Poliovirus vaccine, inactivated (IPV), refer to
Poliovirus Appendix.
* COVID-19 vaccination
Age 19 years or older.
Unvaccinated:
1 dose of updated (2023-2024 Formula) Moderna or Pfizer-BioNTech vaccine.
2-dose series of updated (2023-2024 Formula) Novavax at 0, 3-8 weeks.

Previously vaccinated ‡‡ with 1 or more doses of any COVID-19 vaccine: 1 dose of any
updated (2023-2024 Formula) COVID-19 vaccine administered at least 8 weeks after the most
recent COVID-19 vaccine dose.
Special situations
Persons who are moderately or severely immunocompromised. ††
Unvaccinated:
3-dose series of updated (2023-2024 Formula) Moderna at 0, 4, 8 weeks.
3-dose series of updated (2023-2024 Formula) Pfizer- BioNTech at 0, 3, 7 weeks.
2-dose series of updated (2023-2024 Formula) Novavax at 0, 3 weeks.
Previously vaccinated ‡‡ with 1 dose of any Moderna: 2-dose series of updated (2023-2024
Formula) Moderna at 0, 4 weeks (minimum interval between previous Moderna dose and
dose 1: 4 weeks).
Previously vaccinated ‡‡ with 2 doses of any Moderna: 1 dose of updated (2023-2024
Formula) Moderna at least 4 weeks after most recent dose.
Previously vaccinated ‡‡ with 1 dose of any Pfizer- BioNTech: 2-dose series of updated
(2023-2024 Formula) Pfizer-BioNTech at 0, 4 weeks (minimum interval between previous
Pfizer-BioNTech dose and dose 1: 3 weeks).
Previously vaccinated ‡‡ with 2 doses of any Pfizer- BioNTech: 1 dose of updated (2023-
2024 Formula) Pfizer-BioNTech at least 4 weeks after most recent dose.
Previously vaccinated ‡‡ with 3 or more doses of any Moderna or Pfizer-BioNTech: 1 dose
of any updated (2023-2024 Formula) COVID-19 vaccine at least 8 weeks after the most recent
dose.
Previously vaccinated ‡‡ with 1 or more doses of Janssen or Novavax with or without
dose(s) of any Original monovalent or bivalent COVID-19 vaccine: 1 dose of any updated
(2023-2024 Formula) of COVID-19 vaccine at least 8 weeks after the most recent dose.
There is no preferential recommendation for the use of one COVID-19 vaccine over another
when more than one recommended age-appropriate vaccine is available.
Current COVID-19 vaccine information available at www.cdc.gov/covidschedule. For
information on Emergency Use Authorization (EUA) indications for COVID-19 vaccines, refer
to www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-
19/covid-19-vaccines.
‡‡ Previously vaccinated is defined as having received any Original monovalent or bivalent
COVID-19 vaccine (Janssen, Moderna, Novavax, Pfizer-BioNTech) prior to the updated 2023-
2024 formulation.
†† Persons who are moderately or severely immunocompromised have the option to receive
one additional dose of updated (2023-2024 Formula) COVID-19 vaccine at least 2 months
following the last recommended updated (2023-2024 Formula) COVID-19 vaccine dose.
Further additional updated (2023-2024 Formula) COVID-19 vaccine dose(s) may be
administered, informed by the clinical judgement of a health care provider and personal
preference and circumstances. Any further additional doses should be administered at least
2 months after the last updated (2023-2024 Formula) COVID-19 vaccine dose.
For contraindications and precautions to COVID-19 vaccination, refer to COVID-19 Appendix.
¶ Influenza vaccination
Age 19 years or older: 1 dose any influenza vaccine appropriate for age and health status
annually.
Age 65 years or older: Any one of quadrivalent high-dose inactivated influenza vaccine (HD-
IIV4), quadrivalent recombinant influenza vaccine (RIV4), or quadrivalent adjuvanted
inactivated influenza vaccine (aIIV4) is preferred. If none of these three vaccines is available,
then any other age-appropriate influenza vaccine should be used.
For the 2023-2024 season, refer to www.cdc.gov/mmwr/volumes/72/rr/rr7202a1.htm.
For the 2023-2024 season, refer to the 2024-2025 ACIP influenza vaccine recommendations.
Special situations:
Close contacts (eg, caregivers, health care workers) of severely immunosuppressed
persons who require a protected environment: Should not receive LAIV4. If LAIV4 is given,
they should avoid contact with/caring for such immunosuppressed persons for 7 days after
vaccination.is given, they should avoid contact with/caring for such immunosuppressed
persons for 7 days after vaccination.
NOTE: Persons with an egg allergy can receive any influenza vaccine (egg-based and non-
egg based) appropriate for age and health status.
For contraindications and precautions to influenza vaccination, refer to IIV4 Appendix, LAIV4
Appendix, ccIIV4 Appendix, and RIV4 Appendix.
Δ Respiratory syncytial virus vaccination

Pregnant at 32-36 weeks gestation from September through January in most of the
continental United States (NOTE: Providers in jurisdictions with RSV seasonality that
differs from most of the continental United States [eg, Alaska, jurisdiction with tropical
climate] should follow guidance from public health authorities [eg, CDC, health
departments] or regional medical centers on timing of administration based on local RSV
seasonality. Refer to the 2024 Child and Adolescent Immunization Schedule for
considerations regarding nirsevimab administration to infants): 1 dose RSV vaccine
(Abrysvo™). Administer RSV vaccine regardless of previous RSV infection.
Either maternal RSV vaccination or infant immunization with nirsevimab (RSV
monoclonal antibody) is recommended to prevent respiratory syncytial virus lower
respiratory tract infection in infants.
All other pregnant persons: RSV vaccine not recommended.
There is currently no ACIP recommendation for RSV vaccination in subsequent pregnancies.
No data are available to inform whether additional doses are needed in later pregnancies.
Special situations:
Age 60 years or older: Based on shared clinical decision-making, 1 dose RSV vaccine
(Arexvy® or Abrysvo™). Persons most likely to benefit from vaccination are those
considered to be at increased risk for severe RSV disease (NOTE: Adults age 60 years or
older who are at increased risk for severe RSV disease include those with chronic medical
conditions such as lung diseases [eg, chronic obstructive pulmonary disease, asthma],
cardiovascular diseases [eg, congestive heart failure, coronary artery disease], neurologic or
neuromuscular conditions, kidney disorders, liver disorders, hematologic disorders,
diabetes mellitus, and moderate or severe immune compromise [either attributable to a
medical condition or receipt of immunosuppressive medications or treatment]; those who
are considered to be frail; those of advanced age; those who reside in nursing homes or
other long-term care facilities; and those with other underlying medical conditions or
factors that a health care provider determines might increase the risk of severe respiratory
disease). For additional information on shared clinical decision-making for RSV in older
adults, refer to www.cdc.gov/vaccines/vpd/rsv/downloads/provider-job-aid-for-older-adults-

508.pdf.
For further guidance, refer to www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm.
For contraindications and precautions to Respiratory syncytial virus vaccine (RSV), refer to
RSV Appendix.
◊ Tetanus, diphtheria, and pertussis (Tdap) vaccination

Previously did not receive Tdap at or after age 11 years (NOTE: Tdap administered at age
10 years may be counted as the adolescent dose recommended at age 11-12 years): 1 dose
Tdap, then Td or Tdap every 10 years.
Special situations:
Previously did not receive primary vaccination series for tetanus, diphtheria, or
pertussis: 1 dose Tdap followed by 1 dose Td or Tdap at least 4 weeks later, and a third dose
of Td or Tdap 6 to 12 months later (Tdap can be substituted for any Td dose, but preferred
as first dose), Td or Tdap every 10 years thereafter.
Pregnancy: 1 dose Tdap during each pregnancy, preferably in early part of gestational
weeks 27-36.
Wound management: Persons with 3 or more doses of tetanus-toxoid-containing vaccine:
For clean and minor wounds, administer Tdap or Td if more than 10 years since last dose of
tetanus-toxoid-containing vaccine; for all other wounds, administer Tdap or Td if more than
5 years since last dose of tetanus-toxoid-containing vaccine. Tdap is preferred for persons
who have not previously received Tdap or whose Tdap history is unknown. If a tetanus-
toxoid-containing vaccine is indicated for a pregnant woman, use Tdap. For detailed
information, refer to www.cdc.gov/mmwr/volumes/69/wr/mm6903a5.htm.
For contraindications and precautions to tetanus, diphtheria, and acellular pertussis (Tdap),
refer to Tdap Appendix.
§ Measles, mumps, and rubella vaccination

No evidence of immunity to measles, mumps, or rubella: 1 dose.
Evidence of immunity: Born before 1957 (except for health care personnel, refer
below), documentation of receipt of MMR vaccine, laboratory evidence of immunity or
disease (diagnosis of disease without laboratory confirmation is not evidence of
immunity).
Special situations:
Pregnancy with no evidence of immunity to rubella: MMR contraindicated during
pregnancy; after pregnancy (before discharge from health care facility), 1 dose.
Nonpregnant women of childbearing age with no evidence of immunity to rubella:
1 dose.
HIV infection with CD4 percentages ≥15% and CD4 count ≥200 cells/mm 3 for at
least 6 months and no evidence of immunity to measles, mumps, or rubella: 2-dose
series at least 4 weeks apart; MMR contraindicated for HIV infection with CD4
percentage <15% or CD4 count <200 cells/mm 3 .
Severe immunocompromising conditions: MMR contraindicated.
Students in postsecondary educational institutions, international travelers, and
household or close, personal contacts of immunocompromised persons with no
evidence of immunity to measles, mumps, or rubella: 2-dose series at least 4 weeks
apart if previously did not receive any doses of MMR or 1 dose if previously received 1
dose MMR.
In mumps outbreak settings, for information about additional doses of MMR
(including 3rd dose of MMR), refer to
www.cdc.gov/mmwr/volumes/67/wr/mm6701a7.htm.
Health care personnel:
Born before 1957 with no evidence of immunity to measles, mumps, or rubella:
Consider 2-dose series at least 4 weeks apart for measles or mumps or 1 dose for
rubella.
Born in 1957 or later with no evidence of immunity to measles, mumps, or
rubella: 2-dose series at least 4 weeks apart for measles or mumps or at least 1
dose for rubella.
For contraindications and precautions to measles, mumps, rubella (MMR), refer to MMR
Appendix.
¥ Varicella vaccination
No evidence of immunity to varicella: 2-dose series 4-8 weeks apart if previously did not
receive varicella-containing vaccine (VAR or MMRV [measles-mumps-rubella-varicella
vaccine] for children); if previously received 1 dose varicella-containing vaccine, 1 dose at
least 4 weeks after first dose.
Evidence of immunity: US-born before 1980 (except for pregnant women and health
care personnel [refer below]), documentation of 2 doses varicella-containing vaccine at
least 4 weeks apart, diagnosis or verification of history of varicella or herpes zoster by a
health care provider, laboratory evidence of immunity or disease.
Special situations:
Pregnancy with no evidence of immunity to varicella: VAR contraindicated during
pregnancy; after pregnancy (before discharge from health care facility), 1 dose if previously
received 1 dose varicella-containing vaccine or dose 1 of 2-dose series (dose 2: 4 to 8 weeks
later) if previously did not receive any varicella-containing vaccine, regardless of whether
US-born before 1980.
Health care personnel with no evidence of immunity to varicella: 1 dose if previously
received 1 dose varicella-containing vaccine; 2-dose series 4-8 weeks apart if previously did
not receive any varicella-containing vaccine, regardless of whether US-born before 1980.
HIV infection with CD4 percentages ≥15% and CD4 count ≥200 cells/mm 3 with no
evidence of immunity: Vaccination may be considered (2 doses 3 months apart); VAR
contraindicated for HIV infection with CD4 percentage <15% or CD4 count <200 cells/mm 3 .
Severe immunocompromising conditions: VAR contraindicated.
For contraindications and precautions to varicella (VAR), refer to VAR Appendix.
‡ Zoster vaccination
Age 50 years or older (NOTE: Serologic evidence of prior varicella is not necessary for
zoster vaccination. However, if serologic evidence of varicella susceptibility becomes
available, providers should follow ACIP guidelines for varicella vaccination first. RZV is not
indicated for the prevention of varicella, and there are limited data on the use of RZV in
persons without a history of varicella or varicella vaccination): 2-dose series recombinant
zoster vaccine (RZV, Shingrix) 2-6 months apart (minimum interval: 4 weeks; repeat dose if
administered too soon), regardless of previous herpes zoster or history of zoster vaccine
live (ZVL, Zostavax) vaccination.
Special situations:
Pregnancy: There is currently no ACIP recommendation for RZV use in pregnancy. Consider
delaying RZV until after pregnancy.
Immunocompromising conditions (including persons with HIV regardless of CD4
count; NOTE: If there is no documented history of varicella, varicella vaccination, or herpes
zoster, providers should refer to the clinical considerations for use of RZV in
immunocompromised adults aged ≥19 years and the ACIP varicella vaccine
recommendations for further guidance:
www.cdc.gov/mmwr/volumes/71/wr/mm7103a2.htm): 2-dose series recombinant zoster
vaccine (RZV, Shingrix) 2-6 months apart (minimum interval: 4 weeks; repeat dose if
administered too soon). For detailed information, refer to
www.cdc.gov/shingles/vaccination/immunocompromised-adults.html.
For contraindications and precautions to zoster recombinant vaccine (RZV), refer to RZV
Appendix.
† Human papillomavirus vaccination

All persons up through age 26 years: 2- or 3-dose series depending on age at initial
vaccination or condition.
Age 9-14 years at initial vaccination and received 1 dose or 2 doses less than 5
months apart: 1 additional dose.
Age 9-14 years at initial vaccination and received 2 doses at least 5 months apart:
HPV vaccination series complete, no additional dose needed.
Age 15 years or older at initial vaccination: 3-dose series at 0, 1-2 months, 6 months
(minimum intervals: dose 1 to dose 2: 4 weeks / dose 2 to dose 3: 12 weeks / dose 1 to
dose 3: 5 months; repeat dose if administered too soon).
No additional dose recommended when any HPV vaccine series has been completed using
the recommended dosing intervals.
Shared clinical decision-making:
Adults age 27-45 years: Based on shared clinical decision-making, complete a 2-dose series
(if initiated age 9-14 years) or 3-dose series (if initiated ≥15 years).
For additional information on shared clinical decision-making for HPV; refer to
www.cdc.gov/vaccines/hcp/admin/downloads/isd-job-aid-scdm-hpv-shared-clinical-decision-
making-hpv.pdf.
Special situations:
Age ranges recommended above for routine and catch-up vaccination or shared
clinical decision-making also apply in special situations.
Immunocompromising conditions, including HIV infection: 3-dose series, even for
those who initiate vaccination at age 9 through 14 years.
Pregnancy: Pregnancy testing is not needed before vaccination; HPV vaccination is not
recommended until after pregnancy; no intervention needed if inadvertently vaccinated
while pregnant.
For contraindications and precautions to human papillomavirus (HPV) vaccination, refer to
HPV Appendix.
** Pneumococcal vaccination
Age 65 years or older who have:

Not previously received a dose of PCV13, PCV15, or PCV20 or whose previous
vaccination history is unknown: 1 dose PCV15 or 1 dose PCV20.
If PCV15 is used, administer 1 dose PPSV23 at least 1 year after the PCV15 dose (may
use minimum interval of 8 weeks for adults with an immunocompromising condition
[NOTE: Immunocompromising conditions include chronic renal failure, nephrotic
syndrome, immunodeficiencies, iatrogenic immunosuppression, generalized
malignancy, HIV infection, Hodgkin disease, leukemia, lymphoma, multiple
myeloma, solid organ transplant, congenital or acquired asplenia, or sickle cell
disease or other hemoglobinopathies], cochlear implant, or cerebrospinal fluid leak).
Previously received only PCV7: Follow the recommendation above.
Previously received only PCV13: 1 dose PCV20 or 1 dose PPSV23.
If PCV20 is selected, administer at least 1 year after the PCV13 dose.
If PPSV23 is selected, administer at least 1 year after the last PCV13 dose (may use
minimum interval of 8 weeks for adults with an immunocompromising condition
Previously received only PPSV23: 1 dose PCV15 or 1 dose PCV20. Administer either
PCV15 or PCV20 at least 1 year after the last PPSV23 dose.
If PCV15 is used, no additional PPSV23 doses are recommended.
Previously received both PCV13 and PPSV23 but NO PPSV23 was received at age 65
years or older: 1 dose PCV20 or 1 dose PPSV23.
If PCV20 is selected, administer at least 5 years after the last pneumococcal vaccine
dose.
If PPSV23 is selected, refer to dosing schedule at
cdc.gov/vaccines/vpd/pneumo/downloads/pneumo-vaccine-timing.pdf.
Previously received both PCV13 and PPSV23, AND PPSV23 was received at age 65
years or older: Based on shared clinical decision-making, 1 dose of PCV20 at least 5
years after the last pneumococcal vaccine dose.
For guidance on determining which pneumococcal vaccines a patient needs and when,
please refer to the mobile app which can be downloaded here:
www.cdc.gov/vaccines/vpd/pneumo/hcp/pneumoapp.html.
Special situations:
Age 19-64 years with certain underlying medical conditions or other risk factors who
have (NOTE: Underlying medical conditions or other risk factors include alcoholism, chronic
heart/liver/lung disease, chronic renal failure, cigarette smoking, cochlear implant,
congenital or acquired asplenia, CSF leak, diabetes mellitus, generalized malignancy, HIV,
Hodgkin disease, immunodeficiency, iatrogenic immunosuppression, leukemia, lymphoma,
multiple myeloma, nephrotic syndrome, solid organ transplants, or sickle cell disease, or
other hemoglobinopathies):
Not previously received a PCV13, PCV15, or PCV20 or whose previous vaccination
history is unknown: 1 dose PCV15 or 1 dose PCV20.
If PCV15 is used, administer 1 dose PPSV23 at least 1 year after the PCV15 dose (may
use minimum interval of 8 weeks for adults with an immunocompromising condition

Previously received only PCV7: Follow the recommendation.
Previously received only PCV13: 1 dose PCV20 or 1 dose PPSV23.
If PCV20 is selected, administer at least 1 year after the PCV13 dose.
Previously received only PPSV23: 1 dose PCV15 or 1 dose PCV20. Administer either
PCV15 or PCV20 at least 1 year after the last PPSV23 dose.
If PCV15 is used, no additional PPSV23 doses are recommended.
Previously received PCV13 and 1 dose of PPSV23: 1 dose PCV20 or 1 dose PPSV23.
If PCV20 is selected, administer at least 5 years after the last pneumococcal vaccine
dose.
For guidance on determining which pneumococcal vaccines a patient needs and when,
please refer to the mobile app which can be downloaded here:
www.cdc.gov/vaccines/vpd/pneumo/hcp/pneumoapp.html.
For contraindications and precautions to Pneumococcal conjugate (PCV15 and PCV20), refer
to PCV Appendix; and for Pneumococcal polysaccharide (PPSV23), refer to PPSV23 Appendix.
¶¶ Hepatitis A vaccination
Any person who is not fully vaccinated and requests vaccination (identification of risk
factor not required): 2-dose series HepA (Havrix 6-12 months apart or Vaqta 6-18 months
apart [minimum interval:6 months]) or 3-dose series HepA-HepB (Twinrix at 0,1, 6 months
[minimum intervals: dose 1 to dose 2: 4 weeks / dose 2 to dose 3: 5 months]).
Special situations:
Any person who is not fully vaccinated and who is at risk for hepatitis A virus
infection: 2-dose series HepA or 3-dose series HepA-HepB as above. Risk factors for
hepatitis A virus infection include:
Chronic liver disease (eg, persons with hepatitis B, hepatitis C, cirrhosis, fatty liver
disease, alcoholic liver disease, autoimmune hepatitis, alanine aminotransferase [ALT]
or aspartate aminotransferase [AST] level greater than twice the upper limit of normal).
HIV infection.
Men who have sex with men.
Injection or noninjection drug use.
Persons experiencing homelessness.
Work with hepatitis A virus in research laboratory or with nonhuman primates with
hepatitis A virus infection.
Travel in countries with high or intermediate endemic hepatitis A (HepA-HepB
[Twinrix] may be administered on an accelerated schedule of 3 doses at 0, 7, and 21 to
30 days, followed by a booster dose at 12 months).
Close, personal contact with international adoptee (eg, household or regular
babysitting) in first 60 days after arrival from country with high or intermediate endemic
hepatitis A (administer dose 1 as soon as adoption is planned, at least 2 weeks before
adoptee's arrival).
Pregnancy if at risk for infection or severe outcome from infection during pregnancy.
Settings for exposure, including health care settings targeting services to injection or
noninjection drug users or group homes and nonresidential day care facilities for
developmentally disabled persons (individual risk factor screening not required).
For contraindications and precautions to hepatitis A (HepA) vaccination, refer to HepA
Appendix.
ΔΔ Hepatitis B vaccination
Age 19 through 59 years: Complete a 2- or 3-, or 4-dose series.
2-dose series only applies when 2 doses of Heplisav-B (NOTE: Heplisav-B and PreHevbrio
are not recommended in pregnancy due to lack of safety data in pregnant persons) are
used at least 4 weeks apart.
3-dose series Engerix-B, PreHevbrio (NOTE: Heplisav-B and PreHevbrio are not
recommended in pregnancy due to lack of safety data in pregnant persons), or
Recombivax HB at 0, 1, 6 months (minimum intervals: dose 1 to dose 2: 4 weeks / dose 2
to dose 3: 8 weeks / dose 1 to dose 3: 16 weeks).
3-dose series HepA-HepB (Twinrix at 0, 1, 6 months [minimum intervals: dose 1 to dose
2: 4 weeks / dose 2 to dose 3: 5 months]).
4-dose series HepA-HepB (Twinrix) accelerated schedule of 3 doses at 0, 7, and 21 to 30
days, followed by a booster dose at 12 months.
Age 60 years or older without known risk factors for hepatitis B virus infection may
complete a HepB vaccine series.
Age 60 years or older with known risk factors for hepatitis B virus infection should
complete a HepB vaccine series.
Any adult age 60 years of age or older who requests HepB vaccination should receive a
HepB vaccine series.
Risk factors for hepatitis B virus infection include:
Chronic liver disease (eg, persons with hepatitis C, cirrhosis, fatty liver disease,
alcoholic liver disease, autoimmune hepatitis, alanine aminotransferase [ALT] or
aspartate aminotransferase [AST] level greater than twice upper limit of normal).
HIV infection.
Sexual exposure risk (eg, sex partners of hepatitis B surface antigen [HBsAg]-
positive persons; sexually active persons not in mutually monogamous relationships;
persons seeking evaluation or treatment for a sexually transmitted infection; men
who have sex with men).
Current or recent injection drug use.
Percutaneous or mucosal risk for exposure to blood (eg, household contacts of
HBsAg-positive persons; residents and staff of facilities for developmentally disabled
persons; health care and public safety personnel with reasonably anticipated risk for
exposure to blood or blood-contaminated body fluids; persons on maintenance
dialysis, including in-center or home hemodialysis and peritoneal dialysis, and
persons who are predialysis; patients with diabetes [NOTE: Age 60 years or older
with diabetes: Based on shared clinical decision making, 2-, 3-, or 4-dose series as
above]).
Incarceration.
Travel in countries with high or intermediate endemic hepatitis B.
Special situations:
Patients on dialysis: Complete a 3- or 4-dose series.
3-dose series Recombivax HB at 0, 1, 6 months (NOTE: Use Dialysis Formulation 1 mL =

40 mcg).
4-dose series Engerix-B at 0, 1, 2, and 6 months (NOTE: Use 2 mL dose instead of the
normal adult dose of 1 mL).
For contraindications and precautions to hepatitis B (HepB) vaccination, refer to HepB
Appendix.
◊◊ Meningococcal vaccination
Special situations for MenACWY:
Anatomical or functional asplenia (including sickle cell disease), HIV infection,
persistent complement component deficiency, complement inhibitor (eg, eculizumab,
ravulizumab) use: 2-dose series MenACWY (Menveo or MenQuadfi) at least 8 weeks apart
and revaccinate every 5 years if risk remains.
Travel in countries with hyperendemic or epidemic meningococcal disease, or
microbiologists routinely exposed to Neisseria meningitidis: 1 dose MenACWY (Menveo
or MenQuadfi) and revaccinate every 5 years if risk remains.
First-year college students who live in residential housing (if not previously vaccinated
at age 16 years or older) or military recruits: 1 dose MenACWY (Menveo or MenQuadfi).
For MenACWY booster dose recommendations for groups listed under "Special situations"
and in an outbreak setting (eg, in community or organizational settings or among men who
have sex with men) and additional meningococcal vaccination information, refer to
www.cdc.gov/mmwr/volumes/69/rr/rr6909a1.htm.
Shared clinical decision-making for MenB:
Adolescents and young adults age 16-23 years (age 16-18 years preferred) not at
increased risk for meningococcal disease: Based on shared clinical decision-making, 2-
dose series MenB-4C (Bexsero) at least 1 month apart or 2-dose series MenB-FHbp
(Trumenba) at 0, 6 months (if dose 2 was administered less than 6 months after dose 1,
administer dose 3 at least 4 months after dose 2); MenB-4C and MenB-FHbp are not
interchangeable (use same product for all doses in series).
For additional information on shared clinical decision-making for MenB, refer to
www.cdc.gov/vaccines/hcp/admin/downloads/isd-job-aid-scdm-mening-b-shared-clinical-
decision-making.pdf.
Special situations for MenB:
Anatomical or functional asplenia (including sickle cell disease), persistent
complement component deficiency, complement inhibitor (eg, eculizumab,
ravulizumab) use, or microbiologists routinely exposed to Neisseria meningitidis: 2-
dose primary series MenB-4C (Bexsero) at least 1 month apart or 3-dose primary series
MenB-FHbp (Trumenba) at 0, 1-2, 6 months (if dose 2 was administered at least 6 months
after dose 1, dose 3 not needed; if dose 3 is administered earlier than 4 months after dose
2, a fourth dose should be administered at least 4 months after dose 3); MenB-4C and
MenB-FHbp are not interchangeable (use same product for all doses in series); 1 dose MenB
booster 1 year after primary series and revaccinate every 2-3 years if risk remains.
Pregnancy: Delay MenB until after pregnancy unless at increased risk and vaccination
benefits outweigh potential risks.
For MenB booster dose recommendations for groups listed under "Special situations" and
in an outbreak setting (eg, in community or organizational settings and among men who
have sex with men) and additional meningococcal vaccination information, refer to
www.cdc.gov/mmwr/volumes/69/rr/rr6909a1.htm.
NOTE: MenB vaccines may be administered simultaneously with MenACWY vaccines if

indicated, but at a different anatomic site, if feasible.
Adults may receive a single dose of Penbraya™ as an alternative to separate administration
of MenACWY and MenB when both vaccines would be given on the same clinic day. For
adults not at increased risk, if Penbraya™ is used for dose 1 MenB, MenB-FHbp (Trumenba)
should be administered for dose 2 MenB. For adults at increased risk of meningococcal
disease, Penbraya™ may be used for additional MenACWY and MenB doses (including
booster doses) if both would be given on the same clinic day and at least 6 months have
elapsed since most recent Penbraya™ dose.
For contraindications and precautions to meningococcal ACWY (MenACWY) [MenACWY-CRM
(Menveo); MenACWY-D (Menactra); MenACWY-TT (MenQuadfi)], refer to MenACWY
Appendix.
For contraindications and precautions to meningococcal B (MenB) [MenB-4C (Bexsero);
MenB-FHbp (Trumenba)], refer to MenB Appendix.
§§ Haemophilus influenzae type b vaccination

Special situations:
Anatomical or functional asplenia (including sickle cell disease): 1 dose if previously did
not receive Hib; if elective splenectomy, 1 dose, preferably at least 14 days before
splenectomy.
Hematopoietic stem cell transplant (HSCT): 3-dose series 4 weeks apart starting 6-12
months after successful transplant, regardless of Hib vaccination history.
For contraindications and precautions to Haemophilus influenzae type b (Hib) vaccination,
refer to Hib Appendix.
¥¥ Mpox vaccination
Special situations:
Any person at risk for Mpox infection: 2-dose series, 28 days apart.
Risk factors for Mpox infection include:
Persons who are gay, bisexual, and other MSM, transgender or nonbinary people who in
the past 6 months have had:
A new diagnosis of at least 1 sexually transmitted disease.
More than 1 sex partner.
Sex at a commercial sex venue.
Sex in association with a large public event in a geographic area where Mpox
transmission is occurring.
Persons who are sexual partners of the persons described above.
Persons who anticipate experiencing any of the situations described above.
Pregnancy: There is currently no ACIP recommendation for Jynneos use in pregnancy due
to lack of safety data in pregnant persons. Pregnant persons with any risk factor described
above may receive Jynneos.
Health care personnel: Except in rare circumstances (eg, no available personal protective
equipment), health care personnel who do not have any of the sexual risk factors described
above should not receive Jynneos.
For detailed information, refer to: www.cdc.gov/vaccines/acip/meetings/downloads/slides-
2023-10-25-26/04-MPOX-Rao-508.pdfContraindications and Precautions.
For contraindications and precautions to Mpox, refer to Mpox Appendix.
Reproduced from: Advisory Committee on Immunization Practices. Adult Immunization Schedule by Age, Recommendations
for Ages 19 Years or Older, United States, 2024. Centers for Disease Control and Prevention. Available at:
https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html (Accessed on January 18, 2024).
COVID-19 vaccines available in the United States [1-6]
WITHOUT moderate to WITH

Indicated severe
Name Platform Dose
ages immunocompromising immuno
condition c
Moderna mRNA 6 months 25 mcg For individuals not For indivi

COVID-19 through 4 (0.25 mL previously vaccinated with previously
vaccine (2023- years dark blue- any COVID-19 vaccine * : any COVI
2024 Formula) capped Two vaccine doses 4 Thre
vial) to 8 weeks apart ¶ F
w
5 through 25 mcg For all immunocompetent
T
11 years dose (0.25 individuals in these age
4
mL dark groups:
s
blue- Single vaccine dose (if
capped previously vaccinated,
vial) give at least 8 weeks
after last dose)
12 years 50 mcg
and older (0.5 mL)
Pfizer/BioNTech mRNA 6 months 3 mcg (0.3 For individuals not For indivi
COVID-19 through 4 mL previously vaccinated with previously
vaccine (2023- years Δ yellow- any COVID-19 vaccine * : any COVI
2024 Formula) capped Three vaccine doses: Thre
vial) First two given 3 to F
8 weeks apart ¶ w
Third given at least T
8 weeks after the 8
second s
5 through 10 mcg For all immunocompetent For indivi

11 years (0.3 mL individuals in these age previously
blue- groups: any COVI
capped Single vaccine dose (if Thre
vial) previously vaccinated, F
give at least 8 weeks w
after last dose) T
12 years 30 mcg
4
and older (0.3 mL)
s
Novavax Recombinant 12 years 5 mcg For individuals not

COVID-19 protein, and older spike previously vaccinated with
vaccine (2023- adjuvanted protein/50 any COVID-19 vaccine:
2024 Formula) mcg Two vaccine doses 3
adjuvant to 8 weeks apart ¶
doses (0.5 For individuals who have

mL) received at least one prior
COVID-19 vaccine dose (but
not an updated 2023-2024
formula):
Single vaccine dose at
least 2 months after
last dose
We recommend vaccination with one of these vaccines for eligible individuals. Updated mRNA
vaccines (Moderna COVID-19, 2023-2024 formula and Pfizer-BioNTech COVID-19 vaccine, 2023-2024
formula) are recommended for all vaccine doses. For individuals who cannot or will not take an mRNA
vaccine, the updated Novavax COVID-19 vaccine is an alternative.
CDC: Centers for Disease Control and Prevention; COVID-19: coronavirus disease 2019.
* For individuals younger than five years of age and individuals with moderately to severely
immunocompromising conditions who have already received previous vaccine doses,
recommendations on updated vaccine doses depend on the number of prior vaccines received. If they
have received at least three mRNA vaccine doses, the updated vaccine should be given at least eight
weeks after the most recent dose. Refer to other UpToDate content for details.
¶ Although the FDA authorized intervals for the second doses of the Moderna, Novavax, and Pfizer
COVID-19 bivalent vaccines are four, three, and three weeks after the first dose, respectively, the CDC
suggests an interval up to eight weeks. Extending the interval to eight weeks between vaccine doses
may be preferable for those (especially males aged 12 to 39 years) who have no major comorbidities
and do not need to maximize protection within a shorter period of time; longer intervals may be
associated with a lower risk of myocarditis and slightly improved effectiveness. [5]
Δ Children who turn five years of age during the series should receive all three doses with the
formulation and dose recommended for children six months through four years.
References:
1. SPIKEVAX (COVID-19 Vaccine, mRNA) Suspension for injection, for intramuscular use; 2023-2024 Formula. US Food and
Drug Administration (FDA) approved product information. Revised September 11, 2023. Available at:
https://www.fda.gov/media/155675/download?attachment (Accessed on September 11, 2023).
2. Fact sheet for healthcare providers administering vaccine: Emergency use authorization of Moderna COVID-19 vaccine
(2023-2024 formula), for individuals 6 months through 11 years of age. Available at:
3. COMIRNATY (COVID-19 Vaccine, mRNA) suspension for injection, for intramuscular use; 2023-2024 Formula. US Food
and Drug Administration (FDA) approved product information. Revised September 11, 2023. Available at:
4. Fact sheet for healthcare providers administering vaccine: Emergency use authorization of Pfizer-Biontech COVID-19
vaccine (2023-2024 formula), for 6 months through 11 years of age. Available at:
5. Centers for Disease Control and Prevention. Interim Clinical Considerations for Use of COVID-19 Vaccines Currently
Approved or Authorized in the United States. Available at: https://www.cdc.gov/vaccines/covid-19/clinical-
considerations/covid-19-vaccines-us.html (Accessed on September 17, 2023).
6. US Food and Drug Administration. Emergency use authorization (EUA) of the Novavax COVID-19 vaccine, adjuvanted
(2023-2024 formula), for individuals 12 years or older. Available at: https://www.fda.gov/media/159897/download
(Accessed on October 4, 2023).
Comorbidities the CDC classifies as risk factors for severe COVID-19* [1-3]
Established, probable, and possible risk factors (comorbidities that have been associated with severe
COVID-19 in at least 1 meta-analysis or systematic review, in observational studies, or in case series):
Age ≥65 years ¶
Asthma
Cancer
Cerebrovascular disease
Children with certain underlying conditions Δ
Chronic kidney disease
Chronic lung disease (interstitial lung disease, pulmonary embolism, pulmonary hypertension,
bronchiectasis, COPD)
Chronic liver disease (cirrhosis, non-alcoholic fatty liver disease, alcoholic liver disease,
autoimmune hepatitis)
Cystic fibrosis
Diabetes mellitus, type 1 and type 2
Disabilities (eg, ADHD, cerebral palsy, congenital malformations, limitations with self-care or
activities of daily living, intellectual and developmental disabilities, learning disabilities, spinal cord
injuries)
Heart conditions (such as heart failure, coronary artery disease, or cardiomyopathies)
HIV
Mental health disorders (mood disorders including depression, schizophrenia spectrum disorders
Neurologic conditions (dementia)
Obesity (BMI ≥30 kg/m 2 ) and overweight (BMI 25 to 29 kg/m 2 ), or ≥95 th percentile in children
Physical inactivity
Pregnancy or recent pregnancy
Primary immunodeficiencies
Smoking (current and former)
Sickle cell disease or thalassemia
Solid organ or blood stem cell transplantation
Substance use disorders
Tuberculosis
Use of corticosteroids or other immunosuppressive medications
Possible risk factors but evidence is mixed (comorbidities have been associated with severe COVID-19 in
at least 1 meta-analysis or systematic review, but other studies had reached different conclusions):
Alpha 1 antitrypsin deficiency
Bronchopulmonary dysplasia
Hepatitis B
Hepatitis C
Hypertension
CDC: Centers for Disease Control and Prevention; COVID-19: coronavirus disease 2019; COPD: chronic
obstructive pulmonary disease; ADHD: attention deficit hyperactivity disorder; HIV: human
immunodeficiency virus; BMI: body mass index.
* Listed comorbidities are associated with severe COVID-19 in all adults independent of age. People of
color are also at increased risk of severe disease and death, often at a younger age, due to systemic
health and social inequities.
¶ Risk of severe disease also rises steadily with age, with more than 93% of deaths occurring among
adults ≥50 years and 74% of deaths occurring in adults ≥65 years.
Δ Underlying medical conditions are also associated with severe illness in children, but evidence
implicating specific conditions is limited. Children with the following conditions might be at increased
risk for severe illness: medical complexity; genetic, neurologic, or metabolic conditions; congenital
heart disease; obesity; diabetes; asthma or other chronic lung disease; sickle cell disease;
immunosuppression.
References:
1. Centers for Disease Control and Prevention. Underlying medical conditions associated with high risk for severe COVID-
19: Information for healthcare providers. Available at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-
care/underlyingconditions.html (Accessed on March 1, 2022).
2. Centers for Disease Control and Prevention. Science brief: Evidence used to update the list of underlying medical
conditions that increase a person's risk of severe illness from COVID-19. Available at:
https://stacks.cdc.gov/view/cdc/106171 (Accessed on August 17, 2023).
3. Centers for Disease Control and Prevention. Risk for COVID-19 infection, hospitalization, and death by age group.
Available at: https://stacks.cdc.gov/view/cdc/116835 (Accessed on August 17, 2023).
Guide to discussing hospice care with patients
Identify other "Is there anyone you rely on to help you make important decisions?"
decision makers
"Who in the family should be there with us when we discuss the results?"
Assess "What have your other doctors told you about your condition?"
understanding of
"Have they talked to you about what this latest problem might mean for you?"
prognosis
"From what you know, do you think that over the next month your cancer will get
better, worse, or stay the same?"
Define the "What do you hope for most in the next few months?"
patient's goals
"Is there anything that you're afraid of?"
for care
Reframe goals "I wish we could guarantee that we could keep you alive until your daughter's
graduation, but unfortunately we can't. Perhaps we can work together on a letter
for her to read on that day, so she will know you are there in spirit in case you
cannot be there."
Identify needs "It can be very difficult to care for a family member at home, and no one can do it
for care alone. Have you thought about what kinds of help you might need?"
"Would it help if we could find a way to deliver your medications to you?"
"Would it reassure you if we could send a nurse out to your home to check on
you?"
Summarize and "So I think I understand that your main goal is to stay at home and spend time
link goals with with your family. To do that, we will need to help you in several ways, for instance,
care needs by sending a nurse out to your home and giving you both some help around the
house. Is that right?"
Introduce "One of the best ways to give you the help that you will need to stay at home with
hospice your family is a program called hospice. Have you heard of hospice?"
"Hospice is able to provide more services and support at home than most other
home care programs."
"The hospice team has a lot of experience caring for seriously ill patients at
home."
Respond to emotions elicited and provide closure
Acknowledge "You seemed surprised to learn how sick you are."

response
"I can see it's not easy for you to talk about hospice."
Legitimize "Many people are understandably upset when they learn how ill their loved one is
reaction and that hospice is a possibility."
Empathize "I can imagine how hard this is for both of you; you care about each other so
much."
Explore "Tell me what's upsetting you the most."

concerns
Explain hospice "Hospice doesn't help people die sooner. Hospice helps people die naturally, in
goals their own time."
"Hospice helps people live as well as they can for as long as they can."
Reassure "Hospice's goal is to improve your quality of life as much as possible for whatever
time you have left."
"Hospice can help you and your family make the most of the time you have left."
Reinforce "Let's think this over for a day or two; you know I will continue to care for you
commitment to whatever decision you make."
care
Recommend "I think that hospice would be your best choice right now, but of course, the final
hospice decision is yours."
"Hospice could be very helpful to you in the ways that we've talked about, but I
realize it's a big decision. I'd like to arrange for a hospice nurse to visit you so you
can decide for yourself whether hospice is right for you."
Reproduced with permission from: Casarett DJ, Quill TE. "I'm Not Ready for Hospice": Strategies for Timely and Effective
Hospice Discussions. Ann Intern Med 2007; 146:443. Copyright © 2007 American College of Physicians.
Medical guidelines for determining appropriateness of hospice referral:

Disease-specific guidelines
A patient will be considered to have a life expectancy of 6 months and be eligible for hospice services if
they meet criteria for the following disease-specific baseline guidelines as well as evidence of decline as
outlined in non-disease-specific baseline guidelines (shown on a separate table):
Cancer diagnoses
Disease with metastases at presentation OR
Progression from an earlier stage of disease to metastatic disease with either continued decline in
spite of therapy or patient declines further disease-directed therapy.
NOTE: Certain cancers with poor prognoses (eg, small-cell lung cancer, brain cancer, and pancreatic
cancer) may be hospice eligible without fulfilling the other criteria in this section
Dementia due to Alzheimer disease and related disorders

Patients will be considered to be in the terminal stage of dementia (life expectancy of 6 months or
less) if they meet all of the following criteria:
Stage 7 or beyond according to the Functional Assessment Staging Scale; unable to walk,
dress, and bathe without assistance; urinary and fecal incontinence (intermittent or constant)
no consistently meaningful verbal communication (stereotypical phrases only or the ability to
speak is limited to 6 or fewer intelligible words); AND
At least 1 medical complication within the past 12 months: aspiration pneumonia,

pyelonephritis, septicemia, multiple stage 3 to 4 decubitus ulcers, recurrent fever after
antibiotics, inability to maintain sufficient fluid and calorie intake (≥10% weight loss over
previous 6 months or serum albumin <2.5 g/dL).
NOTE: This section is specific for Alzheimer disease and related disorders and is not appropriate for
other types of dementia.
Heart disease
Patients will be considered to be in the terminal stage of heart disease (life expectancy of 6 months
or less) if they meet the following criteria (1 and 2 should be present; factors from 3 will add
supporting documentation):
1. At the time of initial certification or recertification for hospice, the patient is or has been
already optimally treated for heart disease, or the patient is either not a candidate for surgica
procedures or they decline those procedures. (Optimally treated means that patients who are
not on vasodilators have a medical reason for not being on these drugs, eg, hypotension
or kidney disease.)
2. Patients with congestive heart failure or angina should meet the criteria for the New York
Heart Association (NYHA) Class IV. (Class IV patients with heart disease have an inability to
carry on any physical activity. Symptoms of heart failure or of the anginal syndrome may be
present even at rest. If any physical activity is undertaken, discomfort is increased.) Significant
congestive heart failure may be documented by an ejection fraction of ≤20%, but assessment
of ejection fraction is not required if not already available.
3. Documentation of the following factors supports but is not required to establish eligibility for
hospice care: treatment-resistant symptomatic supraventricular or ventricular arrhythmias,
history of cardiac arrest or resuscitation, history of unexplained syncope, brain embolism of
cardiac origin, or concomitant HIV disease.
HIV disease
Patients will be considered to be in the terminal stage of their illness (life expectancy of 6 months or
less) if they meet the following criteria (1 and 2 should be present; factors from 3 will add supporting
documentation):
1. CD4 count <25 cells per microliter or persistent (2 or more assays at least 1 month apart) viral
load >100,000 copies/mL, plus 1 of the following:
Central nervous system (CNS) lymphoma, untreated or persistent despite treatment;

wasting (loss of at least 10% lean body mass); mycobacterium avium complex (MAC)
bacteremia, untreated, unresponsive to treatment, or treatment refused; progressive
multifocal leukoencephalopathy; systemic lymphoma, with advanced HIV disease and
partial response to chemotherapy; visceral Kaposi sarcoma, unresponsive to therapy; kidney
failure in the absence of dialysis; cryptosporidium infection; toxoplasmosis, unresponsive to
therapy.
2. Decreased performance status, as measured by the Karnofsky Performance Status (KPS) scale
≤50%.
3. Documentation of the following factors will support eligibility for hospice care: chronic
persistent diarrhea for 1 year; persistent serum albumin <2.5 g/dL; concomitant, active
substance abuse; age >50 years; absence of or resistance to effective antiretroviral,
chemotherapeutic, and prophylactic drug therapy related specifically to HIV disease;
advanced AIDS dementia complex; toxoplasmosis; congestive heart failure, symptomatic at
rest; advanced liver disease.
Liver disease
Patients will be considered to be in the terminal stage of liver disease (life expectancy of 6 months o
less) if they meet the following criteria (1 and 2 should be present; factors from 3 will lend
1. Both prolonged prothrombin time (more than 5 seconds over control or INR >1.5) AND serum
albumin <2.5 g/dL.
2. End-stage liver disease with at least 1 of the following: ascites, refractory to treatment or
patient noncompliant; spontaneous bacterial peritonitis; hepatorenal syndrome (elevated
creatinine and BUN with oliguria [<400 mL/day] and urine sodium concentration <10 mEq/L);
hepatic encephalopathy, refractory to treatment or patient noncompliant; recurrent variceal
bleeding, despite intensive therapy.
3. Documentation of the following factors will support eligibility for hospice care: progressive
malnutrition; muscle wasting with reduced strength and endurance; continued active
alcoholism (>80 g ethanol/day); hepatocellular carcinoma; chronic hepatitis B virus infection
(HBsAg-positive); hepatitis C infection, refractory to interferon treatment.
Pulmonary disease
Patients will be considered to be in the terminal stage of pulmonary disease (life expectancy of 6
months or less) if they meet the following criteria. The criteria refer to patients with various forms of
advanced pulmonary disease who eventually follow a final common pathway for end-stage
pulmonary disease (1 and 2 should be present; documentation of 3, 4, and 5 will lend supporting
documentation):
1. Severe chronic lung disease as documented by both of the following:
Disabling dyspnea at rest, poorly responsive or unresponsive to bronchodilators, resulting

in decreased functional capacity, eg, bed to chair existence, fatigue, and cough
(documentation of forced expiratory volume in 1 second [FEV1], <30% predicted value after
bronchodilator, is objective evidence for disabling dyspnea but is not necessary to obtain).
Progression of end-stage pulmonary disease, as evidenced by increasing visits to the
emergency department or hospitalizations for pulmonary infections and/or respiratory
failure or increasing clinician home visits prior to initial certification (documentation of seria
decrease of FEV1 >40 mL/year is objective evidence for disease progression but is not
necessary to obtain).
2. Hypoxemia at rest on room air, as evidenced by pO2 ≤55 mmHg, or oxygen saturation ≤88%,
determined either by arterial blood gases or oxygen saturation monitors (these values may be
obtained from recent hospital records), OR hypercapnia, as evidenced by pCO2 ≥50 mmHg
(this value may be obtained from recent [within 3 months] hospital records).
3. Right heart failure (RHF) secondary to pulmonary disease (Cor pulmonale, eg, not secondary
to left heart disease or valvulopathy).
4. Unintentional progressive weight loss >10% of body weight over the preceding 6 months.
5. Resting tachycardia >100/minute.
Kidney disease (acute and chronic)
Patients will be considered to be in the terminal stage of kidney disease (life expectancy of 6 months
or less) if they meet the following criteria:
Acute kidney failure (1 and either 2, 3, or 4 should be present; factors from 5 will lend
1. The patient is not seeking dialysis or kidney transplant or is discontinuing dialysis. As with
any other condition, an individual with kidney disease is eligible for the hospice benefit if
that individual has a prognosis of 6 months or less, if the illness runs its normal course.
There is no regulation precluding patients on dialysis from electing hospice care. However,
the continuation of dialysis will significantly alter a patient's prognosis and thus potentially
impact that individual's eligibility.
When an individual elects hospice care for end-stage kidney disease (ESKD) or for a
condition to which the need for dialysis is related, the hospice agency is financially
responsible for the dialysis. In such cases, there is no additional reimbursement beyond
the per diem rate. The only situation in which a beneficiary may access both the hospice
benefit and the ESKD benefit is when the need for dialysis is not related to the patient's
terminal illness.
2. Creatinine clearance <10 cc/minute (<15 cc/minute for diabetics), or <15 cc/minute (<20
cc/minute for diabetics) with comorbidity of congestive heart failure.
3. Serum creatinine >8.0 mg/dL (>6.0 mg/dL for diabetics).
4. Estimated glomerular filtration rate (GFR) <10 mL/minute.
5. Comorbid conditions: mechanical ventilation, malignancy (other organ system), chronic

lung disease, advanced cardiac disease, advanced liver disease, immunosuppression/AIDS
albumin <3.5 g/dL, platelet count <25,000/microL, disseminated intravascular coagulation,
gastrointestinal bleeding.
Chronic kidney disease (1 and either 2 or 3 should be present; factors from 4 will lend
1. The patient is not seeking dialysis or kidney transplant or is discontinuing dialysis; as with
any other condition, an individual with kidney disease is eligible for the hospice benefit if
that individual has a prognosis of 6 months or less, if the illness runs its normal course.
There is no regulation precluding patients on dialysis from electing hospice care. However,
the continuation of dialysis will significantly alter a patient's prognosis and thus potentially
impact that individual's eligibility.
When an individual elects hospice care for ESKD or for a condition to which the need for
dialysis is related, the hospice agency is financially responsible for the dialysis. In such
cases, there is no additional reimbursement beyond the per diem rate. The only situation
in which a beneficiary may access both the hospice benefit and the ESKD benefit is when
the need for dialysis is not related to the patient's terminal illness.
2. Creatinine clearance <10 cc/minute (<15 cc/minute for diabetics), or <15 cc/minute (<20
cc/minute for diabetics) with comorbidity of congestive heart failure.
3. Serum creatinine >8.0 mg/dL (>6.0 mg/dL for diabetics).
4. Signs and symptoms of kidney failure: uremia; oliguria (<400 cc/24 hours); intractable
hyperkalemia (>7.0 mEq/L), not responsive to treatment; uremic pericarditis; hepatorenal
syndrome; intractable fluid overload, not responsive to treatment.
Stroke or coma
Patients will be considered to be in the terminal stages of stroke or coma (life expectancy of 6
months or less) if they meet the following criteria:
Stroke:
KPS or Palliative Performance Scale of 40% or less.

Inability to maintain hydration and caloric intake with 1 of the following: weight loss >10%
in the last 6 months or >7.5% in the last 3 months; serum albumin <2.5 g/dL; current
history of pulmonary aspiration, not responsive to speech-language pathology
intervention; sequential calorie counts documenting inadequate caloric/fluid intake;
dysphagia severe enough to prevent the patient from continuing food and fluids necessary
to sustain life, in a patient who does not receive artificial nutrition and hydration.
Coma (any etiology): Comatose patients with any 3 of the following on day 3 of the coma:
abnormal brain stem response, absent verbal response, absent withdrawal response to
pain, serum creatinine >1.5 mg/dL.
Documentation of the following factors will support eligibility for hospice care:
Documentation of medical complications, in the context of progressive clinical decline,

within the previous 12 months, that support a terminal prognosis:
Aspiration pneumonia, upper urinary tract infection (pyelonephritis), refractory stage 3
to 4 decubitus ulcers, fever recurrent after antibiotics.
For stroke patients, documentation of diagnostic imaging factors that support poor
prognosis after stroke include:
For non-traumatic hemorrhagic stroke: large-volume hemorrhage on CT (≥20 mL if
intratentorial, ≥50 mL if supratentorial), ventricular extension of hemorrhage, surface
area of involvement of hemorrhage ≥30% of cerebrum, midline shift ≥1.5 cm,
obstructive hydrocephalus in a patient who declines or is not a candidate for
ventriculoperitoneal shunt. For thrombotic/embolic stroke: large anterior infarcts with
both cortical/subcortical involvement, large bihemispheric infarcts, basilar artery
occlusion, bilateral vertebral artery occlusion.
Amyotrophic lateral sclerosis (ALS)

Patients are considered eligible for hospice care if they do not elect tracheostomy and invasive
ventilation and display evidence of critically impaired respiratory function (with or without use of
noninvasive positive pressure ventilation [NIPPV]) and/or severe nutritional insufficiency (with or
without use of a gastrostomy tube).
Critically impaired respiratory function is as defined by:
Forced vital capacity (FVC) <40% predicted (seated or supine) and 2 or more of the following
symptoms and/or signs: dyspnea at rest, orthopnea, use of accessory respiratory
musculature, paradoxical abdominal motion, respiratory rate >20/minute, reduced
speech/vocal volume, weakened cough, symptoms of sleep-disordered breathing, frequent
awakening, daytime somnolence/excessive daytime sleepiness, unexplained headaches,
unexplained confusion, unexplained anxiety, unexplained nausea.
If unable to perform the FVC test, patients meet this criterion if they manifest 3 or more of the
above symptoms/signs.
Severe nutritional insufficiency is defined as dysphagia with progressive weight loss of at leas
5% of body weight with or without election for gastrostomy tube insertion.
These revised criteria rely less on the measured FVC and, as such, reflect the reality that not a
patients with ALS can or will undertake regular pulmonary function tests.
KPS = 50: Requires considerable assistance and frequent medical care.
KPS <50: Unable to care for self; requires equivalent of institutional or hospital care; disease may be
progressing rapidly.
HIV: human immunodeficiency virus; CD4: cluster of differentiation 4; AIDS: acquired

immunodeficiency syndrome; INR: international normalized ratio; BUN: blood urea nitrogen; HBsAg:
hepatitis B surface antigen; pO2: partial pressure of oxygen; pCO2: partial pressure of carbon dioxide;
CT: computed tomography.
Sources:
1. The NHO medical guidelines for non-cancer disease and local medical review policy: hospice access for patients with
diseases other than cancer. Hosp J 1999.
2. Centers for Medicare & Medicaid Services. Medicare Coverage Database. Available at: https://www.cms.gov/medicare-
coverage-database/details/lcd-details.aspx?LCDId=34538 (Accessed on January 5, 2021).
Stages of radiographic involvement in pulmonary sarcoidosis
Stage Radiographic findings
I Bilateral hilar adenopathy
II Bilateral hilar adenopathy and reticular opacities (predominantly in upper lobes)
III Reticular opacities (predominantly in upper lobes) without hilar lymphadenopathy
IV Reticular opacities, volume loss, conglomerated masses with traction bronchiectasis.

Calcification and cavitation or cyst formation may be present.
Nodular Multiple, bilateral lung nodules and minimal hilar adenopathy

sarcoid
Reference:
1. Scadding JG. Prognosis of intrathoracic sarcoidosis in England: A review of 136 cases after five years' observation. Br
Med J 1961; 2:1165.
Examples of drugs and biologics that can cause interstitial lung disease
Antibiotics Drug-induced systemic lupus
Ethambutol
erythematosus
Minocycline Hydantoins
Nitrofurantoin, acute and chronic Hydralazine
Isoniazid
Anti-inflammatory agents
Penicillamine
Abatacept
Procainamide
Azathioprine*
Cyclophosphamide*
Illicit drugs
Gold Cocaine
Interleukin-1 blockers (anakinra) Heroin
Leflunomide Methadone
Methotrexate* Propoxyphene
Nonsteroidal antiinflammatory agents Talc
Penicillamine Miscellaneous
Rituximab (anti-CD20 monoclonal antibody) Bacille Calmette-Guerin (BCG)
Sulfasalazine Bromocriptine
Thalidomide* Drugs inducing pulmonary infiltrates and

eosinophilia
Tocilizumab
L-tryptophan
Tumor-necrosis factor-alpha blockers
Oxygen
Anti-arrhythmic agents
Radiation
Amiodarone
Statins
Tocainide
Antineoplastic agents
Alkylating agents
Busulfan
Chlorambucil
Cyclophosphamide*
Melphalan
Procarbazine
Antibiotics
Bleomycin sulfate
Mitomycin C
Antimetabolites
Azathioprine*
Cytosine arabinoside
Methotrexate*
Nitrosoureas
BCNU (carmustine)
CCNU (lomustine)
Methyl-CCNU (semustine)
Other
Alpha interferon
Docetaxel
Etoposide (VP-16)
Gefitinib
Nilutamide
Paclitaxel
Temsirolimus
Thalidomide*
* Drugs that are used as both antineoplastic and anti-inflammatory agents.
Adapted from: Camus P. Interstitial lung disease from drugs, biologics, and radiation. In: Interstitial Lung Disease, 5th ed,
Schwarz MI, King TE Jr (Eds), People's Medical Publishing House, Shelton, 2011.

Overview of The Management of Adults With Interstitial Lung Disease

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Overview of The Management of Adults With Interstitial Lung Disease

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23/2/24, 13:54 Overview of the management of adults with interstitial lung disease - UpToDate

Official reprint from UpToDate®

Overview of the management of adults with interstitial

Literature review current through: Jan 2024.

● (See "Treatment of idiopathic pulmonary fibrosis".)

● (See "Acute interstitial pneumonia (Hamman-Rich syndrome)".)

ONGOING MONITORING OF PATIENTS WITH ILD

Following diagnosis, clinical follow-up of patients with ILD involves reassessment of

History and physical examination

● Nonpulmonary symptoms – Systemic and nonpulmonary symptoms may indicate

• Systemic glucocorticoids – Numerous adverse effects are associated with chronic

the identification and prevention of glucocorticoid adverse effects can be found

• Other immunosuppressants – Other immunosuppressant medications commonly

- Pirfenidone – For those receiving pirfenidone, LFTs should be monitored

impairment should be assessed prior to initiation of pirfenidone, and dose

● Surveillance and monitoring of autoantibodies – Monitoring of autoantibodies in

● Surveillance for pulmonary hypertension (PH) – We routinely assess for PH with

Re-evaluating diagnosis or management options — Occasionally, new information during

GENERAL CARE MEASURES FOR PATIENTS WITH ILD

Pulmonary rehabilitation — Although much of the data supporting pulmonary

Prevention of pulmonary infections and acute exacerbations of ILD — Pulmonary

● Vaccination against respiratory infections, including:

• Streptococcus pneumoniae, regardless of age, according to United States Centers

● Early outpatient treatment of respiratory infection – Treatment includes antibiotics

● Evaluation and treatment of recurrent aspiration – Patients with ILD should be

appropriate dietary interventions should be strongly encouraged. Pharmacologic

● Risks of general anesthesia and mechanical ventilation – Mechanical ventilation

Clinical trial information is available at ClinicalTrials.gov.

GENERAL TREATMENT PRINCIPLES

The pharmacologic treatment of ILD typically varies based on diagnosis, predominant

● Exposure-associated ILDs – ILDs arising acutely or subacutely after an environmental

● ILDs characterized by glucocorticoid responsiveness – Cryptogenic organizing

● ILDs with accompanying extrapulmonary manifestations – For ILDs associated with

APPROACH TO THE ILD PATIENT WITH WORSENING PULMONARY

Patients with progressive fibrotic changes or worsening restriction — The development

• 1) Worsening restrictive physiology (absolute decline in forced vital capacity [FVC] ≥5

• 2) Worsening respiratory symptoms, or

• 3) Progression of radiologic fibrosis (increased extent or severity of reticular

● Pirfenidone – Two trials have examined pirfenidone in patients with progression of

● Respiratory infection – Evaluation for respiratory infection commonly includes sputum

● Decompensated heart failure – Weight gain, orthopnea, vascular distribution of

● Aspiration – Acute or recurrent aspiration are common causes of worsening

potentially inciting drug pending further work-up. If no other cause is found, we

● Acute exacerbation of ILD (AE-ILD) – While acute exacerbations are well-described in

As an exception to this approach, cyclophosphamide, rather than high-dose

Patients with fulminant or rapidly progressive ILD associated with dermatomyositis or

high-dose glucocorticoids and concomitant additional immunosuppressants, including

Patients with other ILDs, such as sarcoidosis, hypersensitivity pneumonitis, or

In those with severe AE-ILD requiring hospitalization, shared decision-making around

Worsening air-trapping or obstruction — Patients with ILD can develop worsening

Isolated worsening diffusing capacity — An isolated worsening diffusing capacity or a

After transthoracic echocardiogram evaluation, patients at moderate or high suspicion for

No change in PFTs or chest imaging — Common causes of worsening pulmonary

tachycardia, and breathlessness, especially those of acute onset, without changes on

● Coronary artery disease – Coronary artery disease is a common comorbidity in

● Occult disease progression – As a diagnosis of exclusion, some individuals may

REFERRAL FOR LUNG TRANSPLANTATION EVALUATION

progression [57]. (See "Lung transplantation: An overview" and "Lung transplantation:

Most patients with fibrotic-appearing features of ILD on imaging or pathology are

● Decline in DLCO ≥10 percent predicted during six months of follow-up

● Pulmonary hypertension (PH) on right heart catheterization or transthoracic

● Hospitalization because of respiratory decline, pneumothorax, or acute exacerbation

REFERRAL FOR END-OF-LIFE CARE