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

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.

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.

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 diagnosis can be confirmed by lung biopsy. A videoscopic assisted thoracoscopic wedge biopsy (VATS) under general anesthesia may be necessary to obtain enough tissue to make an accurate diagnosis. This kind of biopsy involves placement of several tubes through the chest wall, one of which is used to cut off a piece of lung to send for evaluation. The removed tissue is examined histopathologically by microscopy to confirm the presence and pattern of fibrosis as well as presence of other features that may indicate a specific cause e.g. specific types of mineral dust or possible response to therapy e.g. a pattern of so-called non-specific interstitial fibrosis.

Misdiagnosis is common because, while overall pulmonary fibrosis is not rare, each individual type of pulmonary fibrosis is uncommon and the evaluation of patients with these diseases is complex and requires a multidisciplinary approach. Terminology has been standardized but difficulties still exist in their application. Even experts may disagree with the classification of some cases.

On spirometry, as a restrictive lung disease, both the FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) are reduced so the FEV1/FVC ratio is normal or even increased in contrast to obstructive lung disease where this ratio is reduced. The values for residual volume and total lung capacity are generally decreased in restrictive lung disease.

Bronchiectasis may be diagnosed clinically or on review of imaging. The British Thoracic Society recommends all non-cystic-fibrosis-related bronchiectasis be confirmed by CT. CT may reveal tree-in-bud abnormalities, dilated bronchi, and cysts with defined borders.

Other investigations typically performed at diagnosis include blood tests, sputum cultures, and sometimes tests for specific genetic disorders.

According to a recent study, the main risk factors for RA-ILD are advancing age, male sex, greater RA disease activity, rheumatoid factor (RF) positivity, and elevated titers of anticitrullinated protein antibodies such as anticyclic citrullinated peptide. Cigarette smoking also appears to increase risk of RA-ILD, especially in patients with human leukocyte antigen DRB1.

A recently published retrospective study by a team from Beijing Chao-Yang Hospital in Beijing, China, supported three of the risk factors listed for RA-ILD and identified an additional risk factor. In that study of 550 RA patients, logistic regression analysis of data collected on the 237 (43%) with ILD revealed that age, smoking, RF positivity, and elevated lactate dehydrogenase closely correlated with ILD.

Recent studies have identified risk factors for disease progression and mortality. A retrospective study of 167 patients with RA-ILD determined that the usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) was a risk factor for progression, as were severe disease upon diagnosis and rate of change in pulmonary function test results in the first 6 months after diagnosis.

A study of 59 RA-ILD patients found no median survival difference between those with the UIP pattern and those without it. But the UIP group had more deaths, hospital admissions, need for supplemental oxygen, and decline in lung function.

Women who are pregnant or couples planning a pregnancy can have themselves tested for the "CFTR" gene mutations to determine the risk that their child will be born with CF. Testing is typically performed first on one or both parents and, if the risk of CF is high, testing on the fetus is performed. The American College of Obstetricians and Gynecologists recommends all people thinking of becoming pregnant be tested to see if they are a carrier.

Because development of CF in the fetus requires each parent to pass on a mutated copy of the "CFTR" gene and because CF testing is expensive, testing is often performed initially on one parent. If testing shows that parent is a "CFTR" gene mutation carrier, the other parent is tested to calculate the risk that their children will have CF. CF can result from more than a thousand different mutations. As of 2016, typically only the most common mutations are tested for, such as ΔF508 Most commercially available tests look for 32 or fewer different mutations. If a family has a known uncommon mutation, specific screening for that mutation can be performed. Because not all known mutations are found on current tests, a negative screen does not guarantee that a child will not have CF.

During pregnancy, testing can be performed on the placenta (chorionic villus sampling) or the fluid around the fetus (amniocentesis). However, chorionic villus sampling has a risk of fetal death of one in 100 and amniocentesis of one in 200; a recent study has indicated this may be much lower, about one in 1,600.

Economically, for carrier couples of cystic fibrosis, when comparing preimplantation genetic diagnosis (PGD) with natural conception (NC) followed by prenatal testing and abortion of affected pregnancies, PGD provides net economic benefits up to a maternal age around 40 years, after which NC, prenatal testing, and abortion have higher economic benefit.

The exact cause of rheumatoid lung disease is unknown. However, associated factors could be due largely to smoking. Sometimes, the medicines used to treat rheumatoid arthritis, especially methotrexate, may result in lung disease.

Prevention's:

- Stop smoking: Chemicals found in cigarettes can irritate already delicate lung tissue, leading to further complications.

- Having regular checkups: The doctor could listen to lungs and monitor breathing, because lung problems that are detected early can be easier to treat.

UIP may be diagnosed by a radiologist using computed tomography (CT) scan of the chest, or by a pathologist using tissue obtained by a lung biopsy. Radiologically, the main feature required for a confident diagnosis of UIP is honeycomb change in the periphery and the lower portions (bases) of the lungs. The histologic hallmarks of UIP, as seen in lung tissue under a microscope by a pathologist, are interstitial fibrosis in a "patchwork pattern", honeycomb change and fibroblast foci (see images below).

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.

In order to prevent bronchiectasis, children should be immunized against measles, pertussis, pneumonia, and other acute respiratory infections of childhood. While smoking has not been found to be a direct cause of bronchiectasis, it is certainly an irritant that all patients should avoid in order to prevent the development of infections (such as bronchitis) and further complications.

Treatments to slow down the progression of this chronic disease include keeping bronchial airways clear and secretions weakened through various forms of pneumotherapy. Aggressively treating bronchial infections with antibiotics to prevent the destructive cycle of infection, damage to bronchial tubes, and more infection is also standard treatment. Regular vaccination against pneumonia, influenza and pertussis are generally advised. A healthy body mass index and regular doctor visits may have beneficial effects on the prevention of progressing bronchiectasis. The presence of hypoxemia, hypercapnia, dyspnea level and radiographic extent can greatly affect the mortality rate from this disease.

The differential diagnosis includes other types of lung disease that cause similar symptoms and show similar abnormalities on chest radiographs. Some of these diseases cause fibrosis, scarring or honeycomb change. The most common considerations include:

- chronic hypersensitivity pneumonitis

- non-specific interstitial pneumonia

- sarcoidosis

- pulmonary Langerhans cell histiocytosis

- asbestosis

Cystic fibrosis may be diagnosed by many different methods, including newborn screening, sweat testing, and genetic testing. As of 2006 in the United States, 10% of cases are diagnosed shortly after birth as part of newborn screening programs. The newborn screen initially measures for raised blood concentration of immunoreactive trypsinogen. Infants with an abnormal newborn screen need a sweat test to confirm the CF diagnosis. In many cases, a parent makes the diagnosis because the infant tastes salty. Immunoreactive trypsinogen levels can be increased in individuals who have a single mutated copy of the "CFTR" gene (carriers) or, in rare instances, in individuals with two normal copies of the "CFTR" gene. Due to these false positives, CF screening in newborns can be controversial. Most U.S. states and countries do not screen for CF routinely at birth. Therefore, most individuals are diagnosed after symptoms (e.g. sinopulmonary disease and GI manifestations) prompt an evaluation for cystic fibrosis. The most commonly used form of testing is the sweat test. Sweat testing involves application of a medication that stimulates sweating (pilocarpine). To deliver the medication through the skin, iontophoresis is used, whereby one electrode is placed onto the applied medication and an electric current is passed to a separate electrode on the skin. The resultant sweat is then collected on filter paper or in a capillary tube and analyzed for abnormal amounts of sodium and chloride. People with CF have increased amounts of them in their sweat. In contrast, people with CF have less thiocyanate and hypothiocyanite in their saliva and mucus (Banfi et al.). In the case of milder forms of CF, transepithelial potential difference measurements can be helpful. CF can also be diagnosed by identification of mutations in the CFTR gene.

People with CF may be listed in a disease registry that allows researchers and doctors to track health results and identify candidates for clinical trials.

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.

New criteria by the ABPA Complicated Asthma ISHAM Working Group suggests a 6-stage criteria for the diagnosis of ABPA, though this is yet to be formalised into official guidelines. This would replace the current gold standard staging protocol devised by Patterson and colleagues. Stage 0 would represent an asymptomatic form of ABPA, with controlled asthma but still fulfilling the fundamental diagnostic requirements of a positive skin test with elevated total IgE (>1000 IU/mL). Stage 6 is an advanced ABPA, with the presence of type II respiratory failure or pulmonary heart disease, with radiological evidence of severe fibrosis consistent with ABPA on a high-resolution CT scan. It must be diagnosed after excluding the other, reversible causes of acute respiratory failure.

Culturing fungi from sputum is a supportive test in the diagnosis of ABPA, but is not 100% specific for ABPA as "A. fumigatus" is ubiquitous and commonly isolated from lung expectorant in other diseases. Nevertheless, between 40–60% of patients do have positive cultures depending on the number of samples taken.

Hypoxia caused by pulmonary fibrosis can lead to pulmonary hypertension, which, in turn, can lead to heart failure of the right ventricle. Hypoxia can be prevented with oxygen supplementation.

Pulmonary fibrosis may also result in an increased risk for pulmonary emboli, which can be prevented by anticoagulants.

Testing for miliary tuberculosis is conducted in a similar manner as for other forms of tuberculosis, although a number of tests must be conducted on a patient to confirm diagnosis. Tests include chest x-ray, sputum culture, bronchoscopy, open lung biopsy, head CT/MRI, blood cultures, fundoscopy, and electrocardiography. The tuberculosis (TB) blood test, also called an Interferon Gamma Release Assay or IGRA, is a way to diagnose latent TB.

A variety of neurological complications have been noted in miliary tuberculosis patients—tuberculous meningitis and cerebral tuberculomas being the most frequent. However, a majority of patients improve following antituberculous treatment. Rarely lymphangitic spread of lung cancer could mimic miliary pattern of tuberculosis on regular chest X-ray.

The tuberculin skin test, commonly used for detection of other forms of tuberculosis, is not useful in the detection of miliary tuberculosis. The tuberculin skin test fails due to the high numbers of false negatives. These false negatives may occur because of higher rates of tuberculin anergy compared to other forms of tuberculosis.

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.

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.

Most cases of aspergilloma do not require treatment. Treatment of diseases which increase the risk of aspergilloma, such as tuberculosis, may help to prevent their formation. In cases complicated by severe hemoptysis or other associated conditions such as pleural empyema or pneumothorax, surgery may be required to remove the aspergilloma and the surrounding lung tissue by doing a lobectomy or other types of resection and thus stop the bleeding. There has been interest in treatment with antifungal medications such as itraconazole, none has yet been shown to reliably eradicate aspergillomata.

Although most fungi — especially "Aspergillus" — fail to grow in healthy human tissue, significant growth may occur in people whose adaptive immune system is compromised, such as those with chronic granulomatous disease, who are undergoing chemotherapy, or who have recently undergone a bone marrow transplantation. Within the lungs of such individuals, the fungal hyphae spread out as a spherical growth. With the restoration of normal defense mechanisms, neutrophils and lymphocytes are attracted to the edge of the spherical fungal growth where they lyse, releasing tissue-digesting enzymes as a normal function. A sphere of the infected lung is thus cleaved from the adjacent lung. This sphere flops around in the resulting cavity and is recognized on x-ray as a fungus ball. This process is beneficial as a potentially serious invasive fungal infection is converted into surface colonization. Although the fungus is inactivated in the process, surgeons may choose to operate to reduce the possibility of bleeding. Microscopic examination of surgically removed recently formed fungus balls clearly shows a sphere of dead lung containing fungal hyphae. Microscopic examination of older lesions reveals mummified tissue which may reveal faint residual lung or hyphal structures.

The fibrosing pattern of NSIP has a five year survival rate of 86% to 92%, while the cellular pattern of NSIP has a 100% five year survival rate. Patients with NSIP(whether cellular or fibrosing), have a better prognosis than those with usual interstitial pneumonia (UIP).

A CT scan of the lungs and histopathology along with a history of working in the flocking industry can diagnose flock worker's lung. A differential diagnosis may also include Sjögren's syndrome and lymphoid interstitial pneumonia. Flock worker's lung may be misdiagnosed as asthma or recurrent pneumonia. Though X-rays may be abnormal, CT scans are more useful as a diagnostic tool in flock worker's lung. Other diagnostic methods may include a transbronchial biopsy or wedge biopsy.