Eosinophilic pneumonia is diagnosed in one of three circumstances: when a complete blood count reveals increased eosinophils and a chest x-ray or computed tomography (CT) identifies abnormalities in the lung, when a biopsy identifies increased eosinophils in lung tissue, or when increased eosinophils are found in fluid obtained by a bronchoscopy (bronchoalveolar lavage [BAL] fluid). Association with medication or cancer is usually apparent after review of a person's medical history. Specific parasitic infections are diagnosed after examining a person's exposure to common parasites and performing laboratory tests to look for likely causes. If no underlying cause is found, a diagnosis of AEP or CEP is made based upon the following criteria. AEP is most likely with respiratory failure after an acute febrile illness of usually less than one week, changes in multiple areas and fluid in the area surrounding the lungs on a chest x-ray, and greater than 25% eosinophils on a BAL. Other typical laboratory abnormalities include an elevated white blood cell count, erythrocyte sedimentation rate, and immunoglobulin G level. Pulmonary function testing usually reveals a restrictive process with reduced diffusion capacity for carbon monoxide. CEP is most likely when the symptoms have been present for more than a month. Laboratory tests typical of CEP include increased blood eosinophils, a high erythrocyte sedimentation rate, iron deficiency anemia, and increased platelets. A chest x-ray can show abnormalities anywhere, but the most specific finding is increased shadow in the periphery of the lung, away from the heart.

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.

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

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.

Rare cases of BOOP have induced with lobar cicatricial atelectasis.

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

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.

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.

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.

This includes:

- Asthma

- Environmental allergic reaction

- Granulomatosis with polyangiitis (Wegner's syndrome)

- Allergic bronchopulmonary aspergillosis

- Churg-Strauss syndrome

- Loeffler's syndrome

- Acute eosinophilic pneumonia

- Chronic eosinophilic pneumonia (Carrington's disease)

- Polyarteritis nodosa

- Parasitic infections

- Tropical pulmonary eosinophilia

- Tuberculosis

- Fungal infection

- Sarcoidosis

- Drug reaction with eosinophilia and systemic symptoms

- Mastocytosis

- Lymphoproliferative hypereosinophilic syndrome

- Myeloproliferative hypereosinophilic syndrome

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.

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).

Lung biopsies can be diagnostic in cases of chronic hypersensitivity pneumonitis, or may help to suggest the diagnosis and trigger or intensify the search for an allergen. The main feature of chronic hypersensitivity pneumonitis on lung biopsies is expansion of the interstitium by lymphocytes accompanied by an occasional multinucleated giant cell or loose granuloma.

When fibrosis develops in chronic hypersensitivity pneumonitis, the differential diagnosis in lung biopsies includes the idiopathic interstitial pneumonias. This group of diseases includes usual interstitial pneumonia, non-specific interstitial pneumonia and cryptogenic organizing pneumonia, among others.

The prognosis of some idiopathic interstitial pneumonias, e.g. idiopathic usual interstitial pneumonia (i.e. idiopathic pulmonary fibrosis), are very poor and the treatments of little help. This contrasts the prognosis (and treatment) for hypersensitivity pneumonitis, which is generally fairly good if the allergen is identified and exposures to it significantly reduced or eliminated. Thus, a lung biopsy, in some cases, may make a decisive difference.

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).

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.

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

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.

A chest x-ray is useful to confirm or rule out a pneumothorax, pulmonary edema, or pneumonia. Spiral computed tomography with intravenous radiocontrast is the imaging study of choice to evaluate for pulmonary embolism.

A number of labs may be helpful in determining the cause of shortness of breath. D-dimer while useful to rule out a pulmonary embolism in those who are at low risk is not of much value if it is positive as it may be positive in a number of conditions that lead to shortness of breath. A low level of brain natriuretic peptide is useful in ruling out congestive heart failure; however, a high level while supportive of the diagnosis could also be due to advanced age, renal failure, acute coronary syndrome, or a large pulmonary embolism.

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.

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.

Radiologic imaging has long been a criterion for diagnosis of ARDS. While original definitions of ARDS specified that correlative chest X-ray findings were required for diagnosis, the diagnostic criteria have been expanded over time to accept CT and ultrasound findings as equally contributory. Generally, radiographic findings of fluid accumulation (pulmonary edema) affecting both lungs and unrelated to increased cardiopulmonary vascular pressure (such as in heart failure) may be suggestive of ARDS.

Ultrasound findings suggestive of ARDS include the following:

- Anterior subpleural consolidations

- Absence or reduction of lung sliding

- “Spared areas” of normal parenchyma

- Pleural line abnormalities (irregular thickened fragmented pleural line)

- Nonhomogeneous distribution of B-lines (a characteristic ultrasound finding suggestive of fluid accumulation in the lungs)

There is ongoing research on the treatment of ARDS by interferon (IFN) beta-1a to aid in preventing leakage of vascular beds. Traumakine (FP-1201-lyo), is a recombinant human IFN beta-1a drug developed by Faron pharmaceuticals, is undergoing international phase-III clinical trials after an open-label, early-phase trial showed a 81% reduction-in-odds of 28-day mortality in ICU patients with ARDS. The drug is known to function by enhancing lung CD73 expression and increasing production of anti-inflammatory adenosine, such that vascular leaking and escalation of inflammation are reduced.

Pneumonia is typically diagnosed based on a combination of physical signs and a chest X-ray. However, the underlying cause can be difficult to confirm, as there is no definitive test able to distinguish between bacterial and non-bacterial origin.

The World Health Organization has defined pneumonia in children clinically based on either a cough or difficulty breathing and a rapid respiratory rate, chest indrawing, or a decreased level of consciousness. A rapid respiratory rate is defined as greater than 60 breaths per minute in children under 2 months old, greater than 50 breaths per minute in children 2 months to 1 year old, or greater than 40 breaths per minute in children 1 to 5 years old. In children, low oxygen levels and lower chest indrawing are more sensitive than hearing chest crackles with a stethoscope or increased respiratory rate. Grunting and nasal flaring may be other useful signs in children less than five years old.

In general, in adults, investigations are not needed in mild cases. There is a very low risk of pneumonia if all vital signs and auscultation are normal. In persons requiring hospitalization, pulse oximetry, chest radiography and blood tests—including a complete blood count, serum electrolytes, C-reactive protein level, and possibly liver function tests—are recommended. Procalcitonin may help determine the cause and support who should receive antibiotics.

The diagnosis of influenza-like illness can be made based on the signs and symptoms; however, confirmation of an influenza infection requires testing. Thus, treatment is frequently based on the presence of influenza in the community or a rapid influenza test.