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

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.

The diagnosis is typically made by clinical examination. Chest X-ray is sometimes useful to exclude bacterial pneumonia, but not indicated in routine cases.

Testing for the specific viral cause can be done but has little effect on management and thus is not routinely recommended. RSV testing by direct immunofluorescence testing on nasopharyngeal aspirate had a sensitivity of 61% and specificity of 89%. Identification of those who are RSV-positive can help for: disease surveillance, grouping ("cohorting") people together in hospital wards to prevent cross infection, predicting whether the disease course has peaked yet, reducing the need for other diagnostic procedures (by providing confidence that a cause has been identified).

Infants with bronchiolitis between the age of two and three months have a second infection by bacteria (usually a urinary tract infection) less than 6% of the time. Preliminary studies have suggested that elevated procalcitonin levels may assist clinicians in determining the presence of bacterial coinfection, which could prevent unnecessary antibiotic use and costs.

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.

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 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.

Prevention of bronchiolitis relies strongly on measures to reduce the spread of the viruses that cause respiratory infections (that is, handwashing, and avoiding exposure to those symptomatic with respiratory infections). In addition to good hygiene an improved immune system is a great tool for prevention. One way to improve the immune system is to feed the infant with breast milk, especially during the first month of life. Immunizations are available for premature infants who meet certain criteria (some cardiac and respiratory disorders) such as Palivizumab (a monoclonal antibody against RSV). Passive immunization therapy requires monthly injections during winter.

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.

Health care professionals are at risk of occupational influenza exposure; during a pandemic influenza, anyone in a close environment is at risk, including those in an office environment.

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.

Tuberculosis is a lung disease endemic in many parts of the world. Health care professionals and prison guards are at high risk for occupational exposure to tuberculosis, since they work with populations with high rates of the disease.

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.

Giving the mother glucocorticoids speeds the production of surfactant. For very premature deliveries, a glucocorticoid is given without testing the fetal lung maturity. The American College of Obstetricians and Gynecologists (ACOG), Royal College of Medicine, and other major organizations have recommended antenatal glucocorticoid treatment for women at risk for preterm delivery prior to 34 weeks of gestation. Multiple courses of glucocorticoid administration, compared with a single course, does not seem to increase or decrease the risk of death or neurodevelopmental disorders of the child.

In pregnancies of greater than 30 weeks, the fetal lung maturity may be tested by sampling the amount of surfactant in the amniotic fluid by amniocentesis, wherein a needle is inserted through the mother's abdomen and uterus. Several tests are available that correlate with the production of surfactant. These include the lecithin-sphingomyelin ratio ("L/S ratio"), the presence of phosphatidylglycerol (PG), and more recently, the surfactant/albumin (S/A) ratio. For the L/S ratio, if the result is less than 2:1, the fetal lungs may be surfactant deficient. The presence of PG usually indicates fetal lung maturity. For the S/A ratio, the result is given as mg of surfactant per gm of protein. An S/A ratio 55 indicates mature surfactant production(correlates with an L/S ratio of 2.2 or greater).

Few data are available about microscopic lesions and the pathophysiology of COVID-19. The main pathological findings at autopsy are:

- Macroscopy: pleurisy, pericarditis, lung consolidation and pulmonary oedema

- Four types of severity of viral pneumonia can be observed:

- minor pneumonia: minor serous exudation, minor fibrin exudation

- mild pneumonia: pulmonary oedema, pneumocyte hyperplasia, large atypical pneumocytes, interstitial inflammation with lymphocytic infiltration and multinucleated giant cell formation

- severe pneumonia: diffuse alveolar damage (DAD) with diffuse alveolar exudates. DAD is the cause of acute respiratory distress syndrome (ARDS) and severe hypoxemia.

- healing pneumonia: organisation of exudates in alveolar cavities and pulmonary interstitial fibrosis

- plasmocytosis in BAL

- Blood: disseminated intravascular coagulation (DIC); leukoerythroblastic reaction

- Liver: microvesicular steatosis

Pulmonary aspiration resulting in pneumonia, in some patients, particularly those with physical limitations, can be fatal.

The rate of BPD varies among institutions, which may reflect neonatal risk factors, care practices (e.g., target levels for acceptable oxygen saturation), and differences in the clinical definitions of BPD.

The WHO has published several testing protocols for the disease. The standard method of testing is real-time reverse transcription polymerase chain reaction (rRT-PCR). The test is typically done on respiratory samples obtained by a nasopharyngeal swab; however, a nasal swab or sputum sample may also be used. Results are generally available within a few hours to two days. Blood tests can be used, but these require two blood samples taken two weeks apart and the results have little immediate value. Chinese scientists were able to isolate a strain of the coronavirus and publish the genetic sequence so laboratories across the world could independently develop polymerase chain reaction (PCR) tests to detect infection by the virus. As of 4 April 2020, antibody tests (which may detect active infections and whether a person had been infected in the past) were in development, but not yet widely used. The Chinese experience with testing has shown the accuracy is only 60 to 70%. The FDA in the United States approved the first point-of-care test on 21 March 2020 for use at the end of that month.

Diagnostic guidelines released by Zhongnan Hospital of Wuhan University suggested methods for detecting infections based upon clinical features and epidemiological risk. These involved identifying people who had at least two of the following symptoms in addition to a history of travel to Wuhan or contact with other infected people: fever, imaging features of pneumonia, normal or reduced white blood cell count or reduced lymphocyte count.

A study asked hospitalized COVID-19 patients to cough into a sterile container, thus producing a saliva sample, and detected virus in eleven of twelve patients using RT-PCR. This technique has the potential of being quicker than a swab and involving less risk to health care workers (collection at home or in the car).

Along with laboratory testing, chest CT scans may be helpful to diagnose COVID-19 in individuals with a high clinical suspicion of infection but is not recommended for routine screening. Bilateral multilobar ground-glass opacities with a peripheral, asymmetric and posterior distribution are common in early infection. Subpleural dominance, crazy paving (lobular septal thickening with variable alveolar filling), and consolidation may appear as the disease progresses.

The lungs are normally protected against aspiration by a series of "protective reflexes" such as coughing and swallowing. Significant aspiration can only occur if the protective reflexes are absent or severely diminished (in neurological disease, coma, drug overdose, sedation or general anesthesia). In intensive care, sitting patients up reduces the risk of pulmonary aspiration and ventilator-associated pneumonia.

Measures to prevent aspiration depend on the situation and the patient. In patients at imminent risk of aspiration, tracheal intubation by a trained health professional provides the best protection. A simpler intervention that can be implemented is to lay the patient on their side in the recovery position (as taught in first aid and CPR classes), so that any vomitus produced by the patient will drain out their mouth instead of back down their pharynx. Some anesthetists will use sodium citrate to neutralize the stomach's low pH and metoclopramide or domperidone (pro-kinetic agents) to empty the stomach.

People with chronic neurological disorders, for example, after a stroke, are less likely to aspirate thickened fluids.

The location of abscesses caused by aspiration depends on the position one is in. If one is sitting or standing up, the aspirate ends up in the posterior basal segment of the right lower lobe. If one is on one's back, it goes to the superior segment of the right lower lobe. If one is lying on the right side, it goes to the posterior segment of the right upper lobe, or the posterior basal segment of the right upper lobe. If one is lying on the left, it goes to the lingula.

There is evidence to show that steroids given to babies less than 8 days old can prevent bronchopulmonary dysplasia. However, the risks of treatment may outweigh the benefits.

It is unclear if starting steroids more than 7 days after birth is harmful or beneficial. It is thus recommended that they only be used in those who cannot be taken off of a ventilator.

The diagnosis is made by the clinical picture and the chest xray, which demonstrates decreased lung volumes (bell-shaped chest), absence of the thymus (after about 6 hours), a small (0.5–1 mm), discrete, uniform infiltrate (sometimes described as a "ground glass" appearance or as of recently described as "diffuse airspace and interstitial opacities") that involves all lobes of the lung, and air-bronchograms (i.e. the infiltrate will outline the larger airways passages which remain air-filled). In severe cases, this becomes exaggerated until the cardiac borders become inapparent (a 'white-out' appearance).

Fungal pneumonia can be diagnosed in a number of ways. The simplest and cheapest method is to culture the fungus from a patient's respiratory fluids. However, such tests are not only insensitive but take time to develop which is a major drawback because studies have shown that slow diagnosis of fungal pneumonia is linked to high mortality. Microscopy is another method but is also slow and imprecise. Supplementing these classical methods is the detection of antigens. This technique is significantly faster but can be less sensitive and specific than the classical methods.

A molecular test based on quantitative PCR is also available from Myconostica. Relying on DNA detection, this is the most sensitive and specific test available for fungi but it is limited to detecting only pneumocystis jirovecii and aspergillus.

Treatment of the underlying cause is required. Endotracheal intubation and mechanical ventilation are required in cases of severe respiratory failure (PaO2 less than 50 mmHg). Respiratory stimulants such as doxapram are rarely used, and if the respiratory failure resulted from an overdose of sedative drugs such as opioids or benzodiazepines, then the appropriate antidote (naloxone or flumazenil, respectively) will be given.

There is tentative evidence that in those with respiratory failure identified before arrival in hospital, continuous positive airway pressure can be useful when started before conveying to hospital.

Some CAP patients require intensive care, with clinical prediction rules such as the pneumonia severity index and CURB-65 guiding the decision to hospitalize. Factors increasing the need for hospitalization include:

- Age greater than 65

- Underlying chronic illnesses

- Respiratory rate greater than 30 per minute

- Systolic blood pressure less than 90 mmHg

- Heart rate greater than 125 per minute

- Temperature below 35 or over 40 °C

- Confusion

- Evidence of infection outside the lung

Laboratory results indicating hospitalization include:

- Arterial oxygen tension less than 60 mm Hg

- Carbon dioxide over 50 mmHg or pH under 7.35 while breathing room air

- Hematocrit under 30 percent

- Creatinine over 1.2 mg/dl or blood urea nitrogen over 20 mg/dl

- White-blood-cell count under 4 × 10^9/L or over 30 × 10^9/L

- Neutrophil count under 1 x 10^9/L

X-ray findings indicating hospitalization include:

- Involvement of more than one lobe of the lung

- Presence of a cavity

- Pleural effusion