Interstitial lung abnormalities

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.

The most common of the spontaneously occurring diffuse parenchymal lung diseases (also known as idiopathic interstitial pneumonias) is idiopathic pulmonary fibrosis (IPF) [6-8], which is a disorder of lung scarring that typically presents with advanced stages of lung remodeling, severely impaired pulmonary function, and a poor prognosis. Other ILDs can also lead to progressive pulmonary fibrosis (PPF) [9,10], which can similarly result in a median survival of less than five years. Now that antifibrotic therapy has been demonstrated to reduce the rate of lung function decline in patients with IPF [11,12] or PPF in the context of other ILDs [9], there is more incentive to identify these diseases at an earlier stage. Evidence from longitudinal patient cohorts demonstrates that many ILDs develop over extended periods, with detectable early progression on chest computed tomography (CT) imaging occurring in people who are asymptomatic or minimally symptomatic.

This topic will review the definitions and terminology of interstitial lung abnormalities (ILA), including their epidemiologic associations, typical radiologic presentation, and prognosis. We will also provide suggestions regarding the initial work-up and management of people identified with these imaging abnormalities. The classification, diagnosis, and management of patients with ILDs, including IPF, are discussed separately.

●(See "Approach to the adult with interstitial lung disease: Clinical evaluation".)

●(See "Approach to the adult with interstitial lung disease: Diagnostic testing".)

●(See "Overview of the management of adults with interstitial lung disease".)

●(See "Clinical manifestations and diagnosis of idiopathic pulmonary fibrosis".)

●(See "Prognosis and monitoring of idiopathic pulmonary fibrosis".)

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

DEFINITION AND RADIOLOGIC FEATURES

●Definition – ILA are defined as chest CT findings suggestive of an underlying interstitial lung disease (ILD) or early stage of pulmonary fibrosis in a person where a disease was not initially suspected [13,14]. ILA are a category of imaging features alone and do not connote other clinical findings. Only a minority of persons who demonstrate ILA go on to receive a diagnosis of ILD [15].

It is important to note that the ILA definition does not inherently imply a limited extent of disease, just that the imaging study was performed when disease was not clinically suspected. As numerous studies have demonstrated, even advanced imaging patterns (eg, a usual interstitial pneumonia [UIP] pattern) can be present in asymptomatic and undiagnosed research participants [16,17].

Other related but less well-defined terms that are sometimes used for early stages of ILD include "subclinical ILD," "preclinical ILD," and "dirty lung." Research in this area is not focused on establishing new clinical entities but rather on the study of "early" ILD, including how to better predict which patients will go on to develop a progressive fibrotic lung disease.

●Radiologic features – To provide a more standard definition for the field going forward, the Fleischner Society issued a position paper on ILA in 2020 [14]. Based on this position paper, ILA were defined as nondependent abnormalities affecting at least 5 percent of any lung zone including one or more of the following:

•Ground-glass abnormalities (image 1)

•Reticular abnormalities (image 2)

•Nonemphysematous cysts (image 3)

•Traction bronchiectasis (image 2 and image 4)

•Honeycombing (image 4)

•Centrilobular nodularity (if accompanying other interstitial findings, see additional information below) (image 5)

Several imaging features or appearances that have sometimes been grouped with ILA in the literature were excluded from this definition. These features that are not considered ILA include the following:

•Centrilobular nodularity alone without other ILA features (image 6)

•Apical scarring suggestive of pleural parenchymal fibroelastosis (image 7) (see "Idiopathic interstitial pneumonias: Classification and pathology", section on 'Idiopathic pleuroparenchymal fibroelastosis')

•Focal paraspinal fibrosis (image 8)

•Dependent lung atelectasis (image 9)

•Mild focal or unilateral findings (less than 5 percent of a lung zone) (image 10)

•Interstitial changes more suggestive of pulmonary edema (image 11)

●Subcategories of ILA – The Fleischner Society position paper [14] recommended dividing ILA into subcategories including:

•Nonsubpleural ILA (including ILA without a predominant subpleural localization) (image 12)

•Subpleural nonfibrotic ILA (including ILA with a predominant subpleural localization without evidence for pulmonary fibrosis) (image 1)

•Subpleural fibrotic ILA (including ILA with a predominant subpleural localization with evidence for pulmonary fibrosis) (image 2 and image 4)

ILA with a nonsubpleural distribution are usually nonprogressive and not associated with increased mortality [14,17]. Although nonfibrotic subpleural ILA may progress, the highest rate of progression occurs in subpleural fibrotic ILA [14,17,18]. In one study, the presence of subpleural reticulation increased the likelihood of progression on subsequent chest CT more than six-fold [17]. (See 'Surveillance for disease progression' below and 'Prognosis' below.)

EPIDEMIOLOGY — 

Most of the demographic, environmental, and genetic factors associated with ILA, including older age, tobacco exposure, the MUC5B promoter variant, and shorter leukocyte telomere length, overlap considerably with those known to be associated with interstitial pulmonary fibrosis (IPF). (See "Clinical manifestations and diagnosis of idiopathic pulmonary fibrosis", section on 'Epidemiology' and "Pathogenesis of idiopathic pulmonary fibrosis", section on 'Genetic predisposition'.)

Numerous research cohorts worldwide have reported on their characterization of chest CT imaging findings, which has given us a much greater understanding of the incidence and prevalence of chest CT imaging findings suggestive of ILA, underlying interstitial lung disease (ILD), or pulmonary fibrosis. While the literature on the epidemiologic associations of ILA is growing, this topic will primarily focus on associations that have been reproducible across different populations.

●Demographics – Arguably the most reproducible association with ILA is advanced age [14]. ILA are felt to be uncommon in most populations under the age of 50. The prevalence of ILA has ranged from 3 to 20 percent in published studies, with higher prevalence seen in smoking and lung cancer screening cohorts [14,19-26]. Overall prevalence of ILA in the adult general population (typically cohorts with a mean age of around 60) is approximately 7 percent [22,27]. While males are more likely to have ILA than females in some studies [20,28,29], this finding is less consistent than the association with advanced age [22,27].

●Pulmonary physiology – Several studies have demonstrated that ILA are associated with relative reductions in lung volumes (measured by either forced vital capacity [FVC] or total lung capacity [TLC]) [21,25]. The degree of these reductions is generally less than one would expect in patients with clinically identified ILD; for example, one meta-analysis demonstrated an average difference in FVC of 2.2 percent predicted [27]. Similarly, many studies have demonstrated that the diffusion capacity of the lung for carbon monoxide (DLCO; a measure of gas exchange) is reduced in those with ILA compared with participants without ILA [21]. Research participants have also been demonstrated to have relative reductions in their exercise capacity (eg, six-minute walk distance) [30].

●Environmental exposures – The most consistent environmental exposure associated with ILA is exposure to tobacco smoke [22,24,25]. Both active (as compared with former) and the amount of tobacco smoke exposure are consistently associated with ILA. Studies of smokers and lung cancer screening cohorts have frequently demonstrated an increased prevalence of ILA, ranging up to 20 percent [25,26]. Additionally, more than one study has demonstrated that environmental exposure to traffic-related pollutants are associated with ILA [31,32]; however, the specific pollutant measured has varied between studies.

●Genetic epidemiology – Genetic epidemiology studies have generally demonstrated overlaps between the associations of IPF and ILA. For example, the MUC5B promoter variant, the genetic variant most strongly associated with familial pulmonary fibrosis and sporadic IPF [33-35], is also the genetic variant most commonly associated with ILA [21]. Additionally, genome-wide association studies have demonstrated there are several additional genetic variants that demonstrate similar associations with IPF and ILA and a few that do not [21]. Finally, polygenic risk scores (which can simultaneously combine the effect of thousands of genetic variants) have also been associated similarly with IPF and ILA [36,37]. These studies provide evidence that at least some of the genetic risk to develop pulmonary fibrosis, regardless of disease extent, shares common genetic determinants.

●Peripheral blood biomarkers – Reduced telomere length, which has been associated with adverse outcomes among IPF patients [38], has been reproducibly associated with ILA [39,40]. Additionally, increased monocyte counts, which have also been associated with adverse outcomes among IPF patients [41], have been associated with ILA in multiple populations [42]. Peripheral blood protein measures such as galectin-3 (GAL3), growth and differentiating factor 15 (GDF15), matrix metalloproteinase 7 (MMP7), and surfactant protein B (SFTPB) have also demonstrated reproducible associations with ILA [43,44].

INITIAL WORK-UP — 

The initial evaluation of a patient with ILA should be focused on determining the degree of clinical involvement (eg, symptoms or pulmonary function decrements), presence of modifiable risk factors (eg, exposures), family history, and the presence of any underlying autoimmune disease.

History and physical examination — The initial evaluation should focus on risk factors for progression of ILA and development of interstitial lung disease (ILD), as well as careful interrogation to determine whether they have previously undiagnosed symptomatic ILD. (See "Approach to the adult with interstitial lung disease: Clinical evaluation".)

●Symptoms – Many people with previously undiagnosed ILD will have symptoms of exertional dyspnea and chronic cough. The cough is typically dry except when there is concomitant chronic bronchitis in those with a heavy smoking history. A careful review of exertional tolerance is useful, especially in sedentary patients who more rarely exert themselves. Most of the time, patients will have attributed occult dyspnea to aging, deconditioning, obesity, or unresolved symptoms following upper or lower respiratory tract infection. Specifically querying a variety of daily tasks can help determine a patient’s level of dyspnea (table 1). In addition to pulmonary symptoms, evaluation for rheumatologic symptoms, including joint pain/swelling, rash, Raynaud phenomenon, myalgias, muscle weakness, pleuritis, dry eyes, and dry mouth, can suggest undiagnosed connective tissue disease.

●Environmental exposures – Thorough review of the home and work environment to identify contributing or precipitating environmental exposures is a critical diagnostic step that can greatly assist in mitigating disease progression in some patients [45-50]. The most frequently contributory exposure is to cigarette smoke, which is linked to ILA itself, idiopathic pulmonary fibrosis (IPF), and several other ILDs (eg, pulmonary Langerhans cell histiocytosis, desquamative interstitial pneumonitis, respiratory bronchiolitis-ILD). Occupational history should include lifelong employment history and known exposures to dusts, gases, and chemicals, as well as any protective measures that were used (table 2A-B). Air pollution appears to be associated with ILA, and this association may be influenced by a person’s underlying genetic risk [51]. Common household or hobby exposures that may result in ILD include pets (especially any birds), down/feathers (eg pillows, duvets, jackets), hot tubs or swimming pools, wood- or metal-working, spray-painting, or mold exposures (air conditioners, humidifiers, evaporative cooling systems, or water damage) (table 3). Family members may occasionally develop disease from "passive" exposure to dusts from the hobby or occupation of another member of the family (eg, asbestosis, berylliosis). (See "Hypersensitivity pneumonitis (extrinsic allergic alveolitis): Epidemiology, causes, and pathogenesis" and "Hypersensitivity pneumonitis (extrinsic allergic alveolitis): Clinical manifestations and diagnosis".)

●Medication and radiation history – A number of medications have been associated with the development of ILD (table 4) [52]. In some cases, the lung disease may not develop or may not be noticed until after the offending agent has been discontinued. Commonly seen agents in clinical practice include amiodarone, nitrofurantoin, bleomycin, immune checkpoint inhibitors, and inhaled illicit substances. Radiation treatments, most commonly for breast or lung cancer, frequently result in focal areas of lung fibrosis and traction bronchiectasis. Although progressive fibrosis is possible, especially in more severe cases, it is relatively infrequent. (See "Radiation-induced lung injury", section on 'Prognosis'.)

●Family history – Family history should include a history of ILD, autoimmune disease, and both personal and familial signs suggestive of short telomere syndrome (ie, early graying, cryptogenic cirrhosis, and bone marrow dyscrasias). Different types of ILD (eg, IPF and nonspecific interstitial pneumonitis) may occur within a single family [53]. (See "Pathogenesis of idiopathic pulmonary fibrosis", section on 'Genetic predisposition'.)

●Physical examination – Pulmonary examination will typically be nonspecific in patients with ILA. Crackles may be heard in overlying areas with imaging abnormalities. Posterior-basilar crackles that disappear after a few deep breaths may be a clue to the presence of atelectasis. In addition to pulmonary examination, a special area of focus should be assessed for possible connective tissue disease. This includes a thorough skin and joint examination, with an assessment of other systems based on clinical suspicion (table 5).

Laboratory testing — Laboratory testing should be guided by the history and physical examination as well as characteristics of the imaging. For those with suspicion for autoimmune disorders based on these factors, we would send a serologic examination, which typically includes antinuclear antibodies, rheumatoid factor, anticyclic citrullinated peptide, creatinine kinase, aldolase, myositis-associated antibodies, Sjögren’s antibodies (SS-A, SS-B), scleroderma antibodies (antitopoisomerase [Scl-70]), and overlap antibodies (PM-1, also known as PM-Scl). (See "Approach to the adult with interstitial lung disease: Diagnostic testing", section on 'Laboratory tests'.)

Individual antibody testing to identify possible sensitization to potential concerning antigens identified by history (eg, feathers, fur, molds) can sometimes be helpful, particularly when the link between the exposure and pulmonary findings is less certain. We do not suggest the use of large antibody panels, as false-positive findings are common.

Telomere length testing should be performed in patients with a personal or family history suggestive of short telomeres. Typically, flow-FISH (multi-color flow cytometry with fluorescence in situ hybridization) is performed on peripheral blood lymphocytes using peptide nucleic acid probes for telomeric DNA (deoxyribonucleic acid) [54]. Average telomere length below the 1^st percentile for age is considered indicative of abnormally short telomeres and is consistent with short telomere syndrome.

Shorter telomere length is associated with more rapid progression of several types of ILD, worsened survival, and adverse outcomes with immunosuppressive treatments in IPF [55]. Patients with ILA on average have shorter telomeres than those without ILA in several different cohorts [56], but whether shorter telomeres are linked to disease progression has not yet been established.

Pulmonary function testing — For all patients with ILA, we recommend obtaining pulmonary function testing including spirometry, lung volumes, and diffusing capacity for carbon monoxide. A significant reduction in diffusing capacity may be the first sign of decreasing lung function prior to changes in forced vital capacity (FVC) or total lung capacity (TLC) [57].

Additional imaging — If the initial CT scan is of poor quality or there is a question about the findings, we recommend proceeding with a high-resolution CT scan of the chest. Similarly, for basilar findings that might be attributable to atelectasis rather than interstitial changes, we recommend obtaining high-resolution prone imaging to help distinguish between these possibilities. Additional imaging modalities, such as endobronchial optical coherence tomography, may be helpful in further characterizing ILA [58]. However, this technology has not yet been validated in large cohorts.

Genetic studies, in selected patients — The most consistent and replicated genetic risk for ILA and ILA progression is increasing copies of the MUC5B genetic polymorphism, similar to what has been shown in both IPF and familial pulmonary fibrosis [33-35]. In patients with a family history of ILD or short telomeres, we suggest genetic counseling and (if covered by insurance) genetic testing for known mutations associated with pulmonary fibrosis to help guide family risk assessment [55,59].

Limited role for invasive pulmonary studies — For most patients with ILA, additional invasive testing is likely to have low diagnostic yield. Exceptions include occasional patients with suspected granulomatous diseases (eg, hypersensitivity pneumonitis or sarcoidosis) or concomitant concern for an infectious or malignant process.

MANAGEMENT AND CLINICAL FOLLOW-UP — 

The literature on the appropriate interval for follow-up of these patients continues to evolve, and there have not yet been any treatment-related clinical trials for patients with ILA. This section will therefore focus on risk mitigation and recommendations based on data from epidemiologic studies.

Reducing risk for disease progression — Modifiable risk factors for ILA progression include reducing exposures and treatment of underlying autoimmune conditions. Smoking cessation is the most important single modifiable risk factor.

●Smoking cessation – Cigarette smoking is the most replicated [22,24,25], modifiable risk factor for the development and progression of ILA. For those patients who are continuing to use tobacco, we counsel smoking cessation and offer referrals to behavioral counseling and prescriptions for pharmacotherapy. The importance of smoking cessation or continued abstinence should be emphasized at the initial and follow-up visits.

●Avoidance of other exposures – If any additional concerning occupational or environmental exposures have been identified based on patient history and laboratory testing, we suggest counseling on the avoidance of the identified exposures. This is particularly important for common or well-established exposures (eg, beryllium, nitrofurantoin, feathers) and in those whose imaging findings are suspicious for hypersensitivity pneumonitis or drug-induced disease.

●Autoimmune disease treatment, in selected patients – In patients with a known history of an autoimmune disease or where a new diagnosis is made during the initial evaluation of a patient with ILA, we recommend treatment of the autoimmune disease in selected patients. Treatment is most appropriate in patients where there is concern that active inflammation is driving the lung disease and in populations where treatment of the autoimmune disease-associated lung disease has been shown to improve outcomes (eg, rheumatoid arthritis) [60]. Engaging in multidisciplinary discussions with rheumatology providers can be helpful in decision making regarding the management of immunomodulator therapies and further disease monitoring.

Exacerbation prevention — Although relatively little is known about the risk of exacerbations in patients with ILA, prevention of respiratory infections and other lung injury is appropriate in an attempt to reduce this potential risk. Reasonable interventions include:

●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 6)

•Respiratory syncytial virus, in individuals 60 years of age and older

(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 – Early outpatient therapy to prevent worsening lower respiratory tract infection includes antibiotics for possible or verified bacterial pneumonia, oseltamivir in the setting of influenza A infection, and nirmatrelvir/ritonavir for COVID-19 (when available). (See "Seasonal influenza in nonpregnant adults: Treatment", section on 'Patients at risk for complications or severe illness' and "COVID-19: Evaluation and management of adults with acute infection in the outpatient setting", section on 'Treatment with COVID-19-specific therapies'.)

●Evaluation and treatment of recurrent aspiration – Like patients with interstitial lung disease (ILD), those with ILA should be surveilled clinically for gastroesophageal reflux or oropharyngeal dysphagia, with a low threshold for formal evaluation [61]. In those with dysphagia, 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.

●Risks of anesthesia and mechanical ventilation – Mechanical ventilation may result in ventilator-induced lung injury; however, aspiration into an unprotected airway may also lead to airway injury and ensuing complications. The balance of risks and benefits to the lung among different anesthetic techniques is typically best left to the attending anesthesiologist. However, for procedures performed under general anesthesia, it is our practice to recommend a lung protective strategy with use of lower tidal volume ventilation.

Surveillance for disease progression — The optimal approach to serial testing for patients with ILA remains unclear.

Based on known associations with poor prognosis [62], we suggest that those with fibrotic changes on imaging (traction bronchiectasis or honeycombing (image 4)) or decrements in pulmonary function testing (ie, reduced forced vital capacity [FVC] or diffusing capacity) in the absence of other known cause (eg, radiation treatment, chronic obstructive pulmonary disease [COPD]) should be considered to have likely ILD. Patients with ILA found to have likely ILD on initial or subsequent evaluations should be referred for presentation at a multidisciplinary discussion (MDD) for confirmation of diagnosis and management considerations. Future disease monitoring should be based on the established diagnosis. Typical monitoring in patients with ILD is discussed elsewhere. (See "Overview of the management of adults with interstitial lung disease", section on 'Ongoing monitoring of patients with ILD'.)

Across general population and lung cancer screening cohorts, the rate of ILA radiographic progression ranges from 20 percent over two years [23] and up to 65 percent over five years [17,63]. CT features associated with progression of ILA include reticular opacities, traction bronchiectasis, honeycombing, lower lobe predominance, and extent of fibrosis [15,17,18,64]. In a longitudinal CT screening cohort from Korea, where participants on average underwent CT scans every two years, the median time to develop a usual interstitial pneumonia (UIP) pattern from ILA was 11.8 years [15].

Additional genetic factors that likely increase the risk of progression include established short telomere syndrome [38,39,65,66] and MUC5B polymorphism [17,33-35].

Based on these findings, we suggest yearly pulmonary function testing (including spirometry and diffusing capacity of carbon monoxide) and repeat CT imaging within 24 to 36 months in patients with any of the following:

●Subpleural predominant interstitial abnormalities (image 1 and image 2)

●Evidence of definite fibrosis, including traction bronchiectasis or honeycombing (image 2 and image 4)

●Short telomere syndrome, based on average peripheral blood lymphocyte telomere length below the 1^st percentile for age (if obtained due to suggestive personal or family history)

●History of familial pulmonary fibrosis

Repeat testing and imaging are also typically appropriate in patients who develop new or worsening pulmonary symptoms.

The imaging criteria and recommendations above are like those adopted by the Fleischner Society [14]. This approach is also supported by recent longitudinal data from South Korea [15], where on average, all participants underwent repeat CT imaging about every 12 to 24 months. It is important to note that this is an evolving field, and future data will hopefully help provide further risk stratification to guide appropriate follow-up intervals.

Patient resources and clinical trials — We encourage interested patients with these diseases to participate in clinical trials of emerging therapies. There are multiple centers in the United States performing either radiographic or genetic screening of family members of patients with fibrotic lung disease. 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.

PROGNOSIS — 

Although ILA are thought to be an early or milder form of interstitial lung disease (ILD), ILA have been consistently associated with a risk of imaging progression and an increased risk of death. Imaging progression occurs in a subset of patients with ILA. Risk factors for both imaging progression and mortality include increased age, male sex, presence of MUC5B promoter polymorphism, increased cigarette smoke exposure, subpleural-predominant disease, and evidence of fibrosis or traction bronchiectasis [14,15,17,18,20,22-24,62,64,67].

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".)

SUMMARY AND RECOMMENDATIONS

●Definition – ILA are defined as chest CT findings suggestive of an underlying interstitial lung disease (ILD) or early stage of pulmonary fibrosis in a person where a disease was not initially suspected. ILA are defined by imaging features alone. (See 'Definition and radiologic features' above.)

●Epidemiology – ILA are associated with advanced age, cigarette smoke exposure, and increased exposure to air pollution. ILA are also associated with increases in respiratory symptoms, decreased pulmonary function (impaired forced vital capacity [FVC] and diffusing capacity of the lung for carbon monoxide), and an increased risk of mortality. Similar to idiopathic pulmonary fibrosis (IPF), the most common genetic risk factor for ILA is increasing copies of the MUC5B promoter polymorphism. (See 'Epidemiology' above.)

●Evaluation

•Clinical assessment – Clinical assessment of patients with ILA is focused on identifying the degree of clinical involvement (eg, symptoms), the presence of modifiable risk factors (eg, exposures), pertinent family history, and the presence of any underlying autoimmune disease. (See 'History and physical examination' above.)

•Laboratory testing – Laboratory testing should be driven by the clinical assessment and family history. (See 'Laboratory testing' above.)

•Pulmonary function testing – For all patients with ILA, we obtain spirometry, lung volumes, and diffusing capacity for carbon monoxide. A significant reduction in diffusing capacity may be the first sign of decreasing lung function prior to changes in FVC or total lung capacity (TLC). (See 'Pulmonary function testing' above.)

•Genetic testing – In patients with a family history of ILD or short telomeres, we suggest genetic counseling and (if covered by insurance) genetic testing for known mutations associated with pulmonary fibrosis to help guide family risk assessment. (See 'Genetic studies, in selected patients' above.)

●Follow-up and management

•Exposure avoidance, including smoking cessation – Cigarette smoking is a critical modifiable risk factor for the development of ILA. For those patients who are continuing to use tobacco, we counsel smoking cessation and offer referrals to behavioral counseling and prescriptions for pharmacotherapy. If any additional concerning occupational or environmental exposures have been identified based on patient history and laboratory testing, we suggest counseling on the avoidance of the identified exposures. (See 'Reducing risk for disease progression' above and "Overview of smoking cessation management in adults".)

•Autoimmune disease treatment, in selected patients – Treatment of autoimmune disease in patients with ILA is most appropriate in patients where there is concern that active inflammation is driving the lung disease and in populations where treatment of the autoimmune disease-associated lung disease has been shown to improve outcomes (eg, rheumatoid arthritis). (See 'Reducing risk for disease progression' above.)

•Exacerbation prevention – Although data are scarce, we counsel preventing lung injury through vaccination against respiratory infections, evaluation and treatment for signs/symptoms of aspiration, and avoidance of injurious modes of mechanical ventilation. (See 'Exacerbation prevention' above and "Overview of the management of adults with interstitial lung disease", section on 'General care measures for patients with ILD'.)

•Ongoing surveillance – Patients with ILA with high-risk features (eg, subpleural predominant disease or fibrotic changes on imaging) should undergo serial pulmonary function and CT imaging every 24 to 36 months to assess for progression to clinically significant ILD. (See 'Surveillance for disease progression' above.)

•Defining progression to ILD – Patients with traction bronchiectasis and/or honeycombing on imaging and decrements in FVC and/or diffusing capacity should be referred for comprehensive clinical evaluation, including multidisciplinary discussion (MDD), for diagnosis and treatment planning. Those with new or worsening pulmonary symptoms should likewise undergo a diagnostic evaluation for ILD. (See 'Surveillance for disease progression' above.)