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.

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.

Respiratory diseases may be investigated by performing one or more of the following tests

- Biopsy of the lung or pleura

- Blood test

- Bronchoscopy

- Chest x-ray

- Computed tomography scan, including high-resolution computed tomography

- Culture of microorganisms from secretions such as sputum

- Ultrasound scanning can be useful to detect fluid such as pleural effusion

- Pulmonary function test

- Ventilation—perfusion scan

Arterial blood gases may reveal hypoxemia when tested in a lab. Respiratory alkalosis may also be present. Peripheral lymphocytosis can be observed. A lung biopsy may also be indicated.

Respiratory disease is a common and significant cause of illness and death around the world. In the US, approximately 1 billion "common colds" occur each year. A study found that in 2010, there were approximately 6.8 million emergency department visits for respiratory disorders in the U.S. for patients under the age of 18. In 2012, respiratory conditions were the most frequent reasons for hospital stays among children.

In the UK, approximately 1 in 7 individuals are affected by some form of chronic lung disease, most commonly chronic obstructive pulmonary disease, which includes asthma, chronic bronchitis and emphysema.

Respiratory diseases (including lung cancer) are responsible for over 10% of hospitalizations and over 16% of deaths in Canada.

In 2011, respiratory disease with ventilator support accounted for 93.3% of ICU utilization in the United States.

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.

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).

The diagnosis is usually suspected following a CT scan. Typical features on CT include solid and sub-solid nodules, ground glass change and reticulation. There may be features of multi-system involvement such as adenopathy and splenomegaly.

The commonest abnormality on lung function testing is a decrease in gas transfer. Both obstructive and restrictive patterns on spirometry have been reported.

The differential diagnosis includes infection, other interstitial lung diseases and malignant disease including lymphoma. Exclusion of infection is therefore an important step in management, but confirmation of the diagnosis requires lung biopsy. In people who have lung disease prior to a diagnosis of CVID, the differential diagnosis includes sarcoidosis. Sarcoid is also characterised by granulomatous involvement of the lung and therefore patients being investigated for sarcoid should have serum immunoglobulins measured to exclude CVID.

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.

Patients presenting with no symptoms, and not affected by the syndrome may not require treatment. Corticosteroids have been reported to be of benefit in select patients. Bronchodilators may assist with breathing issues and resolution may occur with the use of Highly Active Anti-Retroviral Therapy. However, responses to different treatments are widely varied, and no single first line treatment represents the default treatment for lymphocytic interstitial pneumonia.

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).

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.

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.

The diagnosis can be confirmed by the characteristic appearance of the chest x-ray, which shows widespread pulmonary infiltrates, and an arterial oxygen level (PaO) that is strikingly lower than would be expected from symptoms. Gallium 67 scans are also useful in the diagnosis. They are abnormal in approximately 90% of cases and are often positive before the chest x-ray becomes abnormal. The diagnosis can be definitively confirmed by histological identification of the causative organism in sputum or bronchio-alveolar lavage (lung rinse). Staining with toluidine blue, silver stain, periodic-acid schiff stain, or an immunofluorescence assay will show the characteristic cysts. The cysts resemble crushed ping-pong balls and are present in aggregates of 2 to 8 (and not to be confused with "Histoplasma" or "Cryptococcus", which typically do not form aggregates of spores or cells). A lung biopsy would show thickened alveolar septa with fluffy eosinophilic exudate in the alveoli. Both the thickened septa and the fluffy exudate contribute to dysfunctional diffusion capacity which is characteristic of this pneumonia.

"Pneumocystis" infection can also be diagnosed by immunofluorescent or histochemical staining of the specimen, and more recently by molecular analysis of polymerase chain reaction products comparing DNA samples. Notably, simple molecular detection of "Pneumocystis jirovecii" in lung fluids does not mean that a person has "Pneumocystis" pneumonia or infection by HIV. The fungus appears to be present in healthy individuals in the general population.

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.

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

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

Treatment is with corticosteroids and possibly intravenous immunoglobulins.

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.

Classification can be complex, and the combined efforts of clinicians, radiologists, and pathologists can help in the generation of a more specific diagnosis.

Idiopathic interstitial pneumonia can be subclassified based on histologic appearance into the following patterns:

Usual interstitial pneumonia is the most common type.

Lung biopsies performed on patients with NSIP reveal two different disease patterns - cellular and fibrosing - which are associated with different prognoses. The cellular pattern displays chronic inflammation with minimal fibrosis. The fibrosing pattern displays interstitial fibrosis with various inflammation levels. Both patterns are uniform and lack the prominent fibroblastic foci that are found in other types of idiopathic interstitial pneumonia.

The diagnosis is based upon a history of symptoms after exposure to the allergen and clinical tests. A physician may take blood tests, seeking signs of inflammation, a chest X-ray and lung function tests. The sufferer shows a restrictive loss of lung function.

Precipitating IgG antibodies against fungal or avian antigens can be detected in the laboratory using the traditional Ouchterlony immunodiffusion method wherein 'precipitin' lines form on agar plate. The ImmunoCAP technology has replaced this time consuming, labor-intensive method with their automated CAP assays and FEIA (Fluorescence enzyme immunoassay) that can detect IgG antibodies against Aspergillus fumigatus (Farmer's lung or for ABPA) or avian antigens (Bird Fancier's Lung).

Although overlapping in many cases, hypersensitivity pneumonitis may be distinguished from occupational asthma in that it is not restricted to only occupational exposure, and that asthma generally is classified as a type I hypersensitivity. Unlike asthma, hypersensitivity pneumonitis targets lung alveoli rather than bronchi.

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.

Several diseases can present with similar signs and symptoms to pneumonia, such as: chronic obstructive pulmonary disease (COPD), asthma, pulmonary edema, bronchiectasis, lung cancer, and pulmonary emboli. Unlike pneumonia, asthma and COPD typically present with wheezing, pulmonary edema presents with an abnormal electrocardiogram, cancer and bronchiectasis present with a cough of longer duration, and pulmonary emboli presents with acute onset sharp chest pain and shortness of breath.