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.

The specific criteria for diagnosis of CPA are:

Chest X-rays showing one or more lung cavities. There may be a fungal ball present or not.

Symptoms lasting more than 3 months, usually including weight loss, fatigue, cough, coughing blood (haemoptysis) and breathlessness

A blood test or tissue fluid test positive for Aspergillus species

Aspergilloma

An aspergilloma is a fungal mass caused by a fungal infection with Aspergillus species that grows in either scarred lungs or in a pre-existing lung cavity, which may have been caused by a previous infection. Patients with a previous history of tuberculosis, sarcoidosis, cystic fibrosis or other lung disease are most susceptible to an aspergilloma. Aspergillomas may have no specific symptoms but in many patients there is some coughing up of blood called haemoptysis - this may be infrequent and in small quantity, but can be severe and then it requires urgent medical help.

Tests used to diagnose an aspergilloma may include:

- Chest X-ray

- Chest CT

- Sputum culture

- Bronchoscopy or bronchoscopy with lavage (BAL)

- Serum precipitins for aspergillus (blood test to detect antibodies to aspergillus)

Almost all aspergillomas are caused by "Aspergillus fumigatus". In diabetic patients it may be caused by "Aspergillus niger". It is very rarely caused by "Aspergillus flavus", "Aspergillus oryzae", "Aspergillus terreus" or "Aspergillus nidulans".

On chest X-ray and CT, pulmonary aspergillosis classically manifests as a halo sign, and, later, an air crescent sign.

In hematologic patients with invasive aspergillosis, the galactomannan test can make the diagnosis in a noninvasive way. False positive "Aspergillus" galactomannan tests have been found in patients on intravenous treatment with some antibiotics or fluids containing gluconate or citric acid such as some transfusion platelets, parenteral nutrition or PlasmaLyte.

On microscopy, "Aspergillus" species are reliably demonstrated by silver stains, e.g., Gridley stain or Gomori methenamine-silver. These give the fungal walls a gray-black colour. The hyphae of "Aspergillus" species range in diameter from 2.5 to 4.5 µm. They have septate hyphae, but these are not always apparent, and in such cases they may be mistaken for Zygomycota. "Aspergillus" hyphae tend to have dichotomous branching that is progressive and primarily at acute angles of about 45°.

Fungal pneumonia can be treated with antifungal drugs and sometimes by surgical debridement.

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.

Patients with single aspergillomas generally do well with surgery to remove the aspergilloma, and are best given pre-and post-operative antifungal drugs. Often, no treatment is necessary. However, if a patient coughs up blood (haemoptysis), treatment may be required (usually angiography and embolisation, surgery or taking tranexamic acid). Angiography (injection of dye into the blood vessels) may be used to find the site of bleeding which may be stopped by shooting tiny pellets into the bleeding vessel.

For chronic cavitary pulmonary aspergillosis and chronic fibrosing pulmonary aspergillosis, lifelong use of antifungal drugs is usual. Itraconazole and voriconazole are first and second-line anti fungal agents respectively. Posaconazole can be used as third-line agent, for patients who are intolerant of or developed resistance to the first and second-line agents. Regular chest X-rays, serological and mycological parameters as well as quality of life questionnaires are used to monitor treatment progress. It is important to monitor the blood levels of antifungals to ensure optimal dosing as individuals vary in their absorption levels of these drugs.

Chest radiographs (X-ray photographs) often show a pulmonary infection before physical signs of atypical pneumonia are observable at all.

This is occult pneumonia. In general, occult pneumonia is rather often present in patients with pneumonia and can also be caused by "Streptococcus pneumoniae", as the decrease of occult pneumonia after vaccination of children with a pneumococcal vaccine suggests.

Infiltration commonly begins in the perihilar region (where the bronchus begins) and spreads in a wedge- or fan-shaped fashion toward the periphery of the lung field. The process most often involves the lower lobe, but may affect any lobe or combination of lobes.

Eosinophilic pneumonia due to cancer or parasitic infection carries a prognosis related to the underlying illness. AEP and CEP, however, have very little associated mortality as long as intensive care is available and treatment with corticosteroids is given. CEP often relapses when prednisone is discontinued; therefore, some people with CEP require lifelong therapy. Chronic prednisone is associated with many side effects, including increased infections, weakened bones, stomach ulcers, and changes in appearance.

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

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.

The current medical treatments for aggressive invasive aspergillosis include voriconazole and liposomal amphotericin B in combination with surgical debridement.

For the less aggressive allergic bronchopulmonary aspergillosis findings suggest the use of oral steroids for a prolonged period of time, preferably for 6–9 months in allergic aspergillosis of the lungs. Itraconazole is given with the steroids, as it is considered to have a "steroid sparing" effect, causing the steroids to be more effective, allowing a lower dose.,

Other drugs used, such as amphotericin B, caspofungin (in combination therapy only), flucytosine (in combination therapy only), or itraconazole,

are used to treat this fungal infection. However, a growing proportion of infections are resistant to the triazoles. "A. fumigatus", the most commonly infecting species, is intrinsically resistant to fluconazole.

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.

Chest radiography is usually the first test to detect interstitial lung diseases, but the chest radiograph can be normal in up to 10% of patients, especially early on the disease process.

High resolution CT of the chest is the preferred modality, and differs from routine CT of the chest. Conventional (regular) CT chest examines 7–10 mm slices obtained

at 10 mm intervals; high resolution CT examines 1-1.5 mm slices at 10 mm

intervals using a high spatial frequency reconstruction algorithm. The HRCT therefore provides approximately 10 times more resolution than the conventional CT chest, allowing the HRCT to elicit details that cannot otherwise be visualized.

Radiologic appearance alone however is not adequate and should be interpreted in the clinical context, keeping in mind the temporal profile of the disease process.

Interstitial lung diseases can be classified according to radiologic patterns.

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.

Once suspected, the diagnosis of blastomycosis can usually be confirmed by demonstration of the characteristic broad based budding organisms in sputum or tissues by KOH prep, cytology, or histology. Tissue biopsy of skin or other organs may be required in order to diagnose extra-pulmonary disease. Blastomycosis is histologically associated with granulomatous nodules. Commercially available urine antigen testing appears to be quite sensitive in suggesting the diagnosis in cases where the organism is not readily detected. While culture of the organism remains the definitive diagnostic standard, its slow growing nature can lead to delays in treatment of up to several weeks. However, sometimes blood and sputum cultures may not detect blastomycosis.

Mortality rate in treated cases

- 0-2% in treated cases among immunocompetent patients

- 29% in immunocompromised patients

- 40% in the subgroup of patients with AIDS

- 68% in patients presenting as acute respiratory distress syndrome (ARDS)

Mycoplasma is found more often in younger than in older people.

Older people are more often infected by Legionella.

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.

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.

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.

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.

Cryptococcosis is a very subacute infection with a prolonged subclinical phase lasting weeks to months in persons with HIV/AIDS before the onset of symptomatic meningitis. In Sub-Saharan Africa, the prevalence rates of detectable cryptococcal antigen in peripheral blood is often 4–12% in persons with CD4 counts lower than 100 cells/mcL.

Cryptococcal antigen screen and preemptive treatment with fluconazole is cost saving to the healthcare system by avoiding cryptococcal meningitis. The World Health Organization recommends cryptococcal antigen screening in HIV-infected persons entering care with CD4<100 cells/μL. This undetected subclinical cryptococcal (if not preemptively treated with anti-fungal therapy) will often go on to develop cryptococcal meningitis, despite receiving HIV therapy. Cryptococcosis accounts for 20-25% of the mortality after initiating HIV therapy in Africa. What is effective preemptive treatment is unknown, with the current recommendations on dose and duration based on expert opinion. Screening in the United States is controversial, with official guidelines not recommending screening, despite cost-effectiveness and a 3% U.S. cryptococcal antigen prevalence in CD4<100 cells/μL.

As of tissue or discharge are generally unreliable, the diagnosis of mucormycosis tends to be established with a biopsy specimen of the involved tissue.

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.

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.