Investigation is tailored towards the symptoms and signs. A proper and detailed history looking for the occupational exposures, and for signs of conditions listed above is the first and probably the most important part of the workup in patients with interstitial lung disease. Pulmonary function tests usually show a restrictive defect with decreased diffusion capacity (DLCO).

A lung biopsy is required if the clinical history and imaging are not clearly suggestive of a specific diagnosis or malignancy cannot otherwise be ruled out. In cases where a lung biopsy is indicated, a trans-bronchial biopsy is usually unhelpful, and a surgical lung biopsy is often required.

For some types of chILD and few forms adult ILD genetic causes have been identified. These may be identified by blood tests. For a limited number of cases this is a definite advantage, as a precise molecular diagnosis can be done; frequently then there is no need for a lung biopsy. Testing is available for

Bronchoalveolar lavage (BAL) is a well-tolerated diagnostic procedure in ILD. BAL cytology analyses (differential cell counts) should be considered in the evaluation of patients with IPF at the discretion of the treating physician based on availability and experience at their institution. BAL may reveal alternative specific diagnoses: malignancy, infections, eosinophilic pneumonia, histiocytosis X, or alveolar proteinosis. In the evaluation of patients with suspected IPF, the most important application of BAL is in the exclusion of other diagnoses. Prominent lymphocytosis (>30%) generally allows excluding a diagnosis of IPF.

Chest x-rays of affected individuals typically reveal nonspecific alveolar opacities. Diagnosis is generally made by surgical or endoscopic biopsy of the lung, revealing the distinctive pathologic finding. The current gold standard of PAP diagnosis involves histopathological examination of alveolar specimens obtained from bronchoalveolar lavage and transbronchial lung biopsy.

Microscopically, the distal air spaces are filled with a granular, eosinophilic material that is positive with the PAS stain and the PAS diastase stain. The main histomorphologic differential diagnosis is pulmonary edema, which does not have dense bodies.

An ELISA to measure antibodies against GM-CSF has been validated for routine clinical diagnosis of autoimmune PAP.

According to the updated 2011 guidelines, in the absence of a typical UIP pattern on HRCT, a surgical lung biopsy is required for confident diagnosis.

Histologic specimens for the diagnosis of IPF must be taken at least in three different places and be large enough that the pathologist can comment on the underlying lung architecture. Small biopsies, such as those obtained via transbronchial lung biopsy (performed during bronchoscopy) are usually not sufficient for this purpose. Hence, larger biopsies obtained surgically via a thoracotomy or thoracoscopy are usually necessary.

Lung tissue from people with IPF usually show a characteristic histopathologic UIP pattern and is therefore the pathologic counterpart of IPF. Although a pathologic diagnosis of UIP often corresponds to a clinical diagnosis of IPF, a UIP histologic pattern can be seen in other diseases as well, and fibrosis of known origin (rheumatic diseases for example). There are four key features of UIP including interstitial fibrosis in a ‘patchwork pattern’, interstitial scarring, honeycomb changes and fibroblast foci.

Fibroblastic foci are dense collections of myofibroblasts and scar tissue and, together with honeycombing, are the main pathological findings that allow a diagnosis of UIP.

The chest x-ray is distinctive with features that appear similar to an extensive pneumonia, with both lungs showing widespread white patches. The white patches may seem to migrate from one area of the lung to another as the disease persists or progresses. Computed tomography (CT) may be used to confirm the diagnosis. Often the findings are typical enough to allow the doctor to make a diagnosis without ordering additional tests. To confirm the diagnosis, a doctor may perform a lung biopsy using a bronchoscope. Many times, a larger specimen is needed and must be removed surgically.

Plain chest radiography shows normal lung volumes, with characteristic patchy unilateral or bilateral consolidation. Small nodular opacities occur in up to 50% of patients and large nodules in 15%. On high resolution computed tomography, airspace consolidation with air bronchograms is present in more than 90% of patients, often with a lower zone predominance A subpleural or peribronchiolar distribution is noted in up to 50% of patients. Ground glass appearance or hazy opacities associated with the consolidation are detected in most patients.

Pulmonary physiology is restrictive with a reduced diffusion capacity of the lung for carbon monoxide (DCO). Airflow limitation is uncommon; gas exchange is usually abnormal and mild hypoxemia is common. Bronchoscopy with bronchoalveolar lavage reveals up to 40% lymphocytes, along with more subtle increases in neutrophils and eosinophils. In patients with typical clinical and radiographic features, a transbronchial biopsy that shows the pathologic pattern of organizing pneumonia and lacks features of an alternative diagnosis is adequate to make a tentative diagnosis and start therapy. On surgical lung biopsy, the histopathologic pattern is organizing pneumonia with preserved lung architecture; this pattern is not exclusive to BOOP and must be interpreted in the clinical context.

Histologically, cryptogenic organizing pneumonia is characterized by the presence of polypoid plugs of loose organizing connective tissue (Masson bodies) within alveolar ducts, alveoli, and bronchioles.

Rare cases of BOOP have induced with lobar cicatricial atelectasis.

Multiple abnormal laboratory findings have been noted in indium lung. High levels of serum indium have been found in all cases of indium lung. Other abnormal laboratory values that have been found include elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated C-reactive protein, elevated interstitial lung disease markers, and elevated GM-CSF autoantibodies.

CT scanning and radiography can be used to aid in the diagnosis of indium lung. CT abnormalities include ground-glass opacities, interlobular septal thickening, honeycombing, and bronchiectasis.

Pulmonary function tests, arterial blood gases, ventilation perfusion relationships, and O2 diffusing capacity are normal in the initial stages of PAM. As the disease progresses, pulmonary function tests reveal typical features of a restrictive defect with reduced forced vital capacity (FVC) and elevated forced expiratory volume in FEV1/FVC.

On magnetic resonance imaging (MRI), the calcific lesions usually show hypointensity or a signal void on T1- and T2-weighted images.

The major criterion for diagnosis is typically a confirmed surgical biopsy. Minor diagnostic criteria have been proposed for DIPNECH.

- Clinical presentation: woman, between the age of 45 and 67 with cough and/or shortness of breath for 5–10 years

- Pulmonary function: increased residual volume, increased total lung capacity, fixed obstruction, low diffusing capacity of the lung for carbon monoxide that corrects with alveolar volume

- High-resolution CT scan: diffuse pulmonary nodules 4–10 mm, greater than 20 nodules, mosaic attenuation or air trapping in greater than 50% of the lung

- Transbronchial biopsy: proliferation of pulmonary neuroendocrine cells

- Serum markers: elevated serum chromogranin A levels

VALI is most common in patients receiving mechanical ventilation for acute lung injury or acute respiratory distress syndrome (ALI/ARDS).

Possible reasons for predisposition to VALI include:

- An injured lung may be at risk for further injury

- Cyclic atelectasis is particularly common in an injured lung

Although some patients present with normal lung function, pulmonary function tests generally demonstrate fixed airway obstruction with a decreased FEV1 and reduced FEV1/FVC ratio without bronchodilator response. Air trapping is common and leads to increased residual volumes. As the disease progresses, a mixed pattern of obstruction and restriction may develop. In general the obstructive lung disease is slowly progressive with periods of stability.

According to the American Thoracic Society (ATS), the general diagnostic criteria for asbestosis are:

- Evidence of structural pathology consistent with asbestosis, as documented by imaging or histology

- Evidence of causation by asbestos as documented by the occupational and environmental history, markers of exposure (usually pleural plaques), recovery of asbestos bodies, or other means

- Exclusion of alternative plausible causes for the findings

The abnormal chest x-ray and its interpretation remain the most important factors in establishing the presence of pulmonary fibrosis. The findings usually appear as small, irregular parenchymal opacities, primarily in the lung bases. Using the ILO Classification system, "s", "t", and/or "u" opacities predominate. CT or high-resolution CT (HRCT) are more sensitive than plain radiography at detecting pulmonary fibrosis (as well as any underlying pleural changes). More than 50% of people affected with asbestosis develop plaques in the parietal pleura, the space between the chest wall and lungs. Once apparent, the radiographic findings in asbestosis may slowly progress or remain static, even in the absence of further asbestos exposure. Rapid progression suggests an alternative diagnosis.

Asbestosis resembles many other diffuse interstitial lung diseases, including other pneumoconiosis. The differential diagnosis includes idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis, sarcoidosis, and others. The presence of pleural plaquing may provide supportive evidence of causation by asbestos. Although lung biopsy is usually not necessary, the presence of asbestos bodies in association with pulmonary fibrosis establishes the diagnosis. Conversely, interstitial pulmonary fibrosis in the absence of asbestos bodies is most likely not asbestosis. Asbestos bodies in the absence of fibrosis indicate exposure, not disease.

PAP patients, families, and caregivers are encouraged to join the NIH Rare Lung Diseases Consortium Contact Registry. This is a privacy protected site that provides up-to-date information for individuals interested in the latest scientific news, trials, and treatments related to rare lung diseases.

Rapid progression from initial symptoms to respiratory failure is a key feature. An x-ray that shows ARDS is necessary for diagnosis (fluid in the small air sacs (alveoli) in both lungs). In addition, a biopsy of the lung that shows organizing diffuse alveolar damage is required for diagnosis. Other diagnostic tests are useful in excluding other similar conditions, but history, x-ray, and biopsy are essential. These other tests may include basic blood work, blood cultures, and bronchoalveolar lavage.

The clinical picture is similar to ARDS, but AIP differs from ARDS in that the cause for AIP is not known.

VALI does not need to be distinguished from progressive ALI/ARDS because management is the same in both. Additionally, definitive diagnosis of VALI may not be possible because of lack of sign or symptoms.

There are three basic criteria for the diagnosis of CWP:

1. Chest radiography consistent with CWP

2. An exposure history to coal dust (typically underground coal mining) of sufficient amount and latency

3. Exclusion of alternative diagnoses (mimics of CWP)

Symptoms and pulmonary function testing relate to the degree of respiratory impairment but are not part of the diagnostic criteria. As noted above, the chest X-ray appearance for CWP can be virtually indistinguishable from silicosis. Chest CT, particularly high-resolution scanning (HRCT), are more sensitive than plain X-ray for detecting the small round opacities.

In the differential diagnosis (finding the correct diagnosis between diseases that have overlapping features) of some obstructive lung diseases, DPB is often considered. A number of DPB symptoms resemble those found with other obstructive lung diseases such as asthma, chronic bronchitis, and emphysema. Wheezing, coughing with sputum production, and shortness of breath are common symptoms in such diseases, and obstructive respiratory functional impairment is found on pulmonary function testing. Cystic fibrosis, like DPB, causes severe lung inflammation, excess mucus production, and infection; but DPB does not cause disturbances of the pancreas nor the electrolytes, as does CF, so the two diseases are different and probably unrelated. DPB is distinguished by the presence of lesions that appear on X-rays as nodules in the bronchioles of both lungs; inflammation in all tissue layers of the respiratory bronchioles; and its higher prevalence among individuals with East Asian lineage.

DPB and bronchiolitis obliterans are two forms of primary bronchiolitis. Specific overlapping features of both diseases include strong cough with large amounts of often pus-filled sputum; nodules viewable on lung X-rays in the lower bronchi and bronchiolar area; and chronic sinusitis. In DPB, the nodules are more restricted to the respiratory bronchioles, while in OB they are often found in the membranous bronchioles (the initial non-cartilaginous section of the bronchiole, that divides from the tertiary bronchus) up to the secondary bronchus. OB is a bronchiolar disease with worldwide prevalence, while DPB has more localized prevalence, predominantly in Japan. Prior to clinical recognition of DPB in recent years, it was often misdiagnosed as bronchiectasia, COPD, IPF, phthisis miliaris, sarcoidosis or alveolar cell carcinoma.

Positive indications on patient assessment:

- Shortness of breath

- Chest X-ray may show a characteristic patchy, subpleural, bibasilar interstitial infiltrates or small cystic radiolucencies called honeycombing.

Pneumoconiosis in combination with multiple pulmonary rheumatoid nodules in rheumatoid arthritis patients is known as Caplan's syndrome.

Pneumomediastinum is uncommon and occurs when air leaks into the mediastinum. The diagnosis can be confirmed via chest X-ray showing a radiolucent outline around the heart and mediastinum or via CT scanning of the thorax.

Endogenous lipoid pneumonia and non-specific interstitial pneumonitis has been seen prior to the development of pulmonary alveolar proteinosis in a child.

The prevalence of pulmonary interstitial emphysema widely varies with the population studied. In a 1987 study 3% of infants admitted to the neonatal intensive care unit (NICU) developed pulmonary interstitial emphysema.

The diagnosis of DPB requires analysis of the lungs and bronchiolar tissues, which can require a lung biopsy, or the more preferred high resolution computed tomography (HRCT) scan of the lungs. The diagnostic criteria include severe inflammation in all layers of the respiratory bronchioles and lung tissue lesions that appear as nodules within the terminal and respiratory bronchioles in both lungs. The nodules in DPB appear as opaque lumps when viewed on X-rays of the lung, and can cause airway obstruction, which is evaluated by a pulmonary function test, or PFT. Lung X-rays can also reveal dilation of the bronchiolar passages, another sign of DBP. HRCT scans often show blockages of some bronchiolar passages with mucus, which is referred to as the "tree-in-bud" pattern. Hypoxemia, another sign of breathing difficulty, is revealed by measuring the oxygen and carbon dioxide content of the blood, using a blood test called arterial blood gas. Other findings observed with DPB include the proliferation of lymphocytes (white blood cells that fight infection), neutrophils, and foamy histiocytes (tissue macrophages) in the lung lining. Bacteria such as "H. influenzae" and "P. aeruginosa" are also detectable, with the latter becoming more prominent as the disease progresses. The white blood, bacterial and other cellular content of the blood can be measured by taking a complete blood count (CBC). Elevated levels of IgG and IgA (classes of immunoglobulins) may be seen, as well as the presence of rheumatoid factor (an indicator of autoimmunity). Hemagglutination, a clumping of red blood cells in response to the presence of antibodies in the blood, may also occur. Neutrophils, beta-defensins, leukotrienes, and chemokines can also be detected in bronchoalveolar lavage fluid injected then removed from the bronchiolar airways of individuals with DPB, for evaluation.