# Interstitial Lung Disease

Interstitial lung disease requires early separation of infection, drug toxicity, exposure-related disease, autoimmune ILD, and idiopathic pulmonary fibrosis through high-resolution CT, pulmonary function testing, exposure history, serology, and multidisciplinary review to direct treatment and monitor progression.

**Clinical question:** How should clinicians evaluate, classify, monitor, and escalate care for suspected fibrotic interstitial lung disease?

Updated: 2026-08-24T18:20:09.393719+00:00

## What matters in practice
- Obtain high-resolution chest CT and pulmonary function testing early; HRCT pattern recognition determines whether UIP/IPF is likely and whether tissue sampling may add value. [6][8][17]
- Do not label ILD idiopathic before systematically assessing medication exposure, occupational or environmental antigens, and connective-tissue disease features; chronic hypersensitivity pneumonitis and CTD-ILD can mimic UIP-pattern disease. [7][19]
- A radiologic UIP pattern with no alternative clinical explanation can support IPF after multidisciplinary review; uncertain clinical-radiologic cases may require lung biopsy consideration. [6][7][8]
- Track symptoms, FVC, DLCO, and serial HRCT when clinically indicated; progressive pulmonary fibrosis is identified by worsening across these domains over follow-up. [5][9]
- For confirmed IPF, antifibrotic therapy with pirfenidone or nintedanib is initial disease-modifying treatment, alongside pulmonary rehabilitation, smoking cessation, oxygen when needed, and early transplant or palliative-care consideration. [6]

## Establish whether the presentation is acute, chronic, or acutely worsened

Separate a new diffuse lung process from progression of established fibrotic disease before assigning an ILD subtype.

In a patient with new or worsening dyspnea, cough, hypoxemia, or diffuse parenchymal abnormalities, first determine whether the clinical tempo is acute, subacute, or chronic and compare with prior chest imaging, HRCT, spirometry, lung volumes, and DLCO. A restrictive physiology or reduced DLCO supports physiologic impairment but does not establish a specific ILD diagnosis; HRCT is the pivotal imaging study for defining the diffuse parenchymal pattern. [12][14]

Treat acute deterioration in a patient with established fibrotic ILD as a separate diagnostic event rather than automatically as fibrosis progression. Acute exacerbations in rheumatoid arthritis-associated ILD have been associated with very high mortality, and acute worsening plus FVC decline are mortality-associated events in IPF. Obtain an updated HRCT and reassess competing causes of deterioration before attributing decline to the underlying ILD alone. [21][22]

Document resting and exertional oxygen requirement, symptom trajectory, smoking history, medication chronology, prior thoracic irradiation or inhalational exposures, occupational exposures, home antigen exposures, and systemic autoimmune features. This history determines whether the leading branch is exposure-associated ILD, CTD-ILD, medication-related disease, or an idiopathic interstitial pneumonia; chronic hypersensitivity pneumonitis is a key alternative diagnosis in a fibrotic presentation. [7][19]
- Obtain HRCT rather than relying on chest radiography to characterize a suspected interstitial pattern. [12]
- Obtain baseline spirometry, lung volumes, and DLCO for physiologic staging and later trend assessment. [13][14]
- Refer diagnostically difficult, progressive, or biopsy-considered cases for ILD multidisciplinary discussion integrating clinical, radiologic, and pathologic data. [6][7][13][16]

*Initial branches in suspected fibrotic ILD. [6][7][19]*

| Clinical-imaging branch | Discriminator to obtain | Immediate diagnostic consequence |
| --- | --- | --- |
| Probable IPF/UIP-spectrum disease | HRCT categorized as UIP, probable UIP, indeterminate for UIP, or alternative diagnosis; exclude another clinical cause. [6][8] | Submit clinical and HRCT findings to multidisciplinary review; a radiologic UIP pattern may establish IPF without surgical biopsy when no alternative process is identified. [6][7] |
| Exposure-associated fibrotic ILD | Focused environmental, occupational, and antigen exposure history; evaluate HRCT for features that change the differential toward hypersensitivity pneumonitis. [7][17][19] | Prioritize exposure identification and avoidance; do not assume UIP-pattern fibrosis is idiopathic. [7][19] |
| Connective-tissue disease-associated ILD | Review systemic manifestations and directed autoimmune testing in conjunction with HRCT and pulmonary physiology. [5][13] | Coordinate pulmonary and rheumatologic classification because disease behavior and treatment strategy differ from IPF. [5][13] |
| Unclassifiable or discordant ILD | Identify discordance among clinical history, HRCT, and physiology after expert review. [6][8][16] | Consider whether histopathology would change diagnosis or management before pursuing surgical biopsy or transbronchial cryobiopsy. [6][8][16] |

## Use HRCT pattern to narrow the diagnosis and decide on tissue sampling

HRCT should be interpreted as a diagnostic pattern, not as a generic label of fibrosis.

Classify suspected IPF imaging using the four HRCT categories refined in the 2018 ATS/ERS/JRS/ALAT diagnostic framework: UIP, probable UIP, indeterminate for UIP, and alternative diagnosis. The category determines the confidence of IPF diagnosis and whether additional pathology is potentially informative. [8]

A UIP-pattern distribution is typically basal-predominant, with reticulation and honeycombing increasing from apex to base; traction bronchiectasis and honeycombing also carry prognostic information in ILD. Conversely, air trapping and subpleural sparing are HRCT signs that can redirect the differential away from straightforward IPF toward alternative ILD patterns. [17][24]

When the clinical context contains no alternative cause and HRCT demonstrates UIP, IPF can usually be confirmed through multidisciplinary review without surgical lung biopsy. Histopathology should be considered when clinical and radiologic data leave meaningful diagnostic uncertainty and when a tissue result would alter management. [6][7]
- Request expert thoracic-radiology review of HRCT when the report does not assign a recognized ILD pattern or when exposure history and CT interpretation conflict. [8][16][17]
- Do not treat probable UIP as an automatic mandate for surgery: ATS/ERS/JRS/ALAT guidance conditionally supported surgical lung biopsy in selected patients, whereas Fleischner guidance recommended against routine biopsy in newly detected IIP with probable UIP. [8]
- Use tissue sampling selectively after multidisciplinary discussion; cryobiopsy protocols have lacked standardized specifications for size, number, and sampling locations. [16]

### Pathology and multidisciplinary review

The value of surgical lung biopsy or transbronchial cryobiopsy is highest when the pretest differential remains consequential after HRCT and clinical evaluation—for example, when distinguishing IPF/UIP from chronic hypersensitivity pneumonitis or another fibrotic ILD would change therapeutic direction. Histologic UIP must be interpreted with exposure and autoimmune context because UIP is a pattern, not synonymous with idiopathic disease. [7][19]
- Avoid biopsy when the expected result is unlikely to alter diagnosis or management after expert clinical-radiologic review. [6][7]
- Include pulmonology, thoracic radiology, and pathology in multidisciplinary diagnosis when available; this approach is central to IPF confirmation without biopsy and to resolving complex ILD classification. [6][7][13][16]

*HRCT features that alter the fibrotic ILD differential. [8][17]*

| HRCT feature | Interpretation | Diagnostic action |
| --- | --- | --- |
| Basal-predominant reticulation and honeycombing | Supports a UIP-pattern fibrotic process when paired with compatible distribution and clinical context. [17] | Classify within the UIP/probable UIP/indeterminate/alternative-diagnosis framework and review for secondary causes before diagnosing IPF. [8] |
| Traction bronchiectasis | Supports fibrotic architectural distortion and contributes to radiologic severity assessment. [17][24] | Compare extent on serial HRCT with prior studies when progression is suspected. [24] |
| Air trapping | Can narrow the differential toward diagnoses other than straightforward IPF/UIP. [17] | Revisit exposure history and assess for chronic hypersensitivity pneumonitis in multidisciplinary review. [7][19] |
| Subpleural sparing | Can exclude or reduce the likelihood of some UIP-pattern diagnostic possibilities. [17] | Do not assign IPF solely from fibrosis; pursue alternative-pattern interpretation. [8][17] |

## Distinguish idiopathic, exposure-related, and autoimmune fibrotic ILD

Etiology changes both treatment selection and the meaning of a UIP pattern.

Diagnose IPF only after excluding an alternative disease process. IPF is a chronic progressive fibrosing interstitial pneumonia of unknown etiology defined by radiologic and/or histopathologic UIP; in the appropriate clinical setting, multidisciplinary review of HRCT can establish the diagnosis without biopsy. [6][7]

For suspected hypersensitivity pneumonitis, make a structured antigen and exposure assessment central to the workup, then integrate the exposure history with HRCT and, when needed, pathology. Chronic hypersensitivity pneumonitis is an important pathologic and clinical mimic of IPF/UIP, so an apparent UIP pattern does not end the exposure evaluation. [7][19]

For possible CTD-ILD, use systemic history, examination, directed autoimmune evaluation, HRCT pattern, and pulmonary physiology together rather than relying on a single serologic result. In Sjögren syndrome-associated ILD, UIP pattern was more frequent among patients meeting progressive pulmonary fibrosis criteria than among nonprogressors in one cohort, illustrating that a UIP pattern can occur in autoimmune ILD and may identify higher-risk disease behavior. [5]
- Classify the patient as IPF only when no medication, exposure, autoimmune, or other clinical explanation better accounts for the fibrotic ILD. [6][7]
- If autoimmune disease or an exposure is plausible, preserve that etiologic diagnosis even when HRCT or pathology shows UIP-pattern fibrosis. [5][7][19]
- Use longitudinal behavior in addition to baseline diagnosis: UIP radiologic pattern is associated with worse prognosis across ILD subtypes. [2]

*Etiologic classification determines the next management conversation. [5][6][7][19]*

| Working diagnosis | Evidence that supports it | Decision consequence |
| --- | --- | --- |
| Idiopathic pulmonary fibrosis | No alternative disease process plus radiologic and/or histopathologic UIP; multidisciplinary confirmation is usual. [6][7] | Initiate an IPF-specific antifibrotic discussion and assess supportive, transplant, and palliative-care needs early. [6] |
| Chronic hypersensitivity pneumonitis | Relevant exposure history integrated with HRCT and, where needed, pathology. [7][19] | Identify and eliminate the relevant antigen exposure and avoid misclassification as idiopathic disease. [19] |
| CTD-ILD | Connective-tissue disease context plus ILD identified through HRCT, pulmonary function testing, and multidisciplinary assessment. [5][13] | Coordinate pulmonary-rheumatologic treatment and monitor for progressive pulmonary fibrosis. [5] |
| Unclassifiable fibrotic ILD | Persistent uncertainty after integrated clinical, radiologic, and pathologic review. [16] | Follow symptoms, physiology, and imaging for a progressive phenotype and reconsider tissue only if it would change management. [9][16] |

## Identify progressive pulmonary fibrosis with multidomain follow-up

Progression is a longitudinal clinical-radiologic-physiologic determination rather than a single isolated test result.

At baseline, document symptoms, FVC, DLCO, and HRCT extent/pattern so that subsequent change can be judged against an interpretable reference. Across fibrotic ILDs other than IPF, progression occurs in an estimated 18% to 32% of patients; IPF is intrinsically progressive over time. [9]

Use serial symptoms, pulmonary function, and imaging together. The ATS progressive pulmonary fibrosis framework applied in Sjögren-associated ILD defines progression within 1 year by at least two of three domains: worsening symptoms, physiologic decline, and radiologic progression. In that cohort, physiologic progression was FVC decline of at least 5% and/or DLCO decline of at least 10%. [5]

Interpret FVC decline in clinical context. A decline of at least 10% in FVC and at least 15% in DLCO has also been used as a PFT progression definition in ILD research, illustrating that thresholds vary across studies and should not replace integrated review of symptoms and HRCT. [3][5][9]

Escalate reassessment when symptoms worsen, FVC or DLCO falls, oxygen needs rise, or HRCT shows expanding fibrosis. In addition to confirming progression, search for superimposed triggers or alternate causes of deterioration before changing long-term ILD therapy. [5][21][22][24]
- At each follow-up, compare current FVC and DLCO with prior values rather than relying on a single percent-predicted measurement. [3][5][9]
- Obtain interval HRCT when clinical or physiologic change creates uncertainty about radiologic progression or an alternate cause of worsening. [5][24]
- Treat a UIP radiologic pattern as a prognostic risk marker across ILD subtypes, not solely as an IPF diagnostic label. [2]

*Practical progression framework for fibrotic ILD. [3][5][9]*

| Follow-up domain | Concerning change | Next action |
| --- | --- | --- |
| Symptoms | Worsening respiratory symptoms within 1 year. [5] | Reassess oxygen requirement, compare physiology, and obtain imaging when the cause is not clear. [5][22] |
| FVC | At least 5% decline was used in the ATS-derived PPF framework; at least 10% decline is another research progression threshold. [3][5] | Confirm trend, assess concurrent symptoms and HRCT, and determine whether progression criteria are met. [5][9] |
| DLCO | At least 10% decline was used in the ATS-derived PPF framework; at least 15% decline is another research progression threshold. [3][5] | Interpret with imaging and clinical status rather than as an isolated progression diagnosis. [5][9] |
| HRCT | Radiologic progression paired with worsening symptoms or functional decline supports PPF within 1 year. [5] | Review images longitudinally with thoracic radiology and reconsider disease classification or treatment strategy. [5][24] |

## Start disease-modifying and supportive management without delaying advanced-care planning

Treatment in IPF combines antifibrotic therapy with symptom-directed and advanced-care interventions.

For confirmed IPF, initial disease-modifying therapy is an antifibrotic agent: pirfenidone or nintedanib. Choice should be individualized through discussion of adverse-effect tolerance, comorbidities, drug interactions, treatment burden, and patient goals; the diagnostic label should be secure because IPF-directed therapy follows exclusion of alternative fibrotic ILD causes. [6]

Nerandomilast, an oral phosphodiesterase-4 inhibitor, is an FDA-approved IPF treatment and reduced FVC decline versus placebo over 1 year in a randomized phase 3 trial. Incorporate it through an IPF-specific medication review, with selection and monitoring based on current prescribing information and patient-specific factors. [6]

Prescribe smoking cessation support, pulmonary rehabilitation, and supplemental oxygen when indicated as parallel management rather than as substitutes for antifibrotic treatment. Discuss lung-transplant referral and palliative-care involvement early, including for patients receiving active disease-modifying therapy. [6]
- Confirm IPF through multidisciplinary clinical-radiologic assessment before initiating an IPF-specific treatment pathway. [6][7]
- Monitor FVC, DLCO, symptoms, exercise-related oxygen needs, and HRCT when change in disease behavior is suspected. [5][9]
- Revisit transplant eligibility and goals-of-care planning with clinically meaningful decline, increasing oxygen needs, or progressive fibrotic disease despite treatment. [6]

*Core management elements after IPF confirmation. [6]*

| Management domain | Action | Clinical purpose |
| --- | --- | --- |
| Antifibrotic therapy | Offer pirfenidone or nintedanib as initial therapy. [6] | Disease-modifying treatment for IPF. [6] |
| Newer pharmacotherapy | Consider FDA-approved oral nerandomilast within an IPF medication plan. [6] | A phase 3 trial showed less FVC decline than placebo at 1 year. [6] |
| Functional support | Implement smoking cessation, pulmonary rehabilitation, and supplemental oxygen when indicated. [6] | Address modifiable risk, exercise limitation, and hypoxemia. [6] |
| Advanced care | Discuss early lung-transplant referral and palliative-care options. [6] | Plan for progressive disease while active treatment continues. [6] |

## Common questions

### When is lung biopsy appropriate in suspected IPF?

Consider surgical biopsy when clinical and HRCT findings remain diagnostically uncertain and pathology would change management. UIP-pattern HRCT with no alternative cause can support IPF without biopsy after multidisciplinary review; probable UIP is an area of guideline disagreement and should be individualized. [6][7][8]

### Can a UIP pattern establish idiopathic pulmonary fibrosis in a patient with autoimmune disease or exposure history?

No. UIP is a radiologic and histopathologic pattern that can occur in chronic hypersensitivity pneumonitis and CTD-ILD. Establish IPF only after alternative etiologies are excluded through exposure, medication, autoimmune, imaging, and multidisciplinary assessment. [5][6][7][19]

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## Editorial note

Prepared from cited clinical literature using Astra's research workflow. Verify recommendations against current guidance and patient-specific factors.