Respiratory infections are attributed to a wide range of pathogens, of which fungi are responsible for a minority of cases. However, fungal organisms present a threat in immunosuppressed patients [1]. Moreover, predisposing factors include AIDS, hematological malignancy, organ transplantation, neutropenia, chronic use of corticosteroids and other immunosuppressive therapy, congenital immune deficiency syndromes, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and other underlying lung conditions [2].

Fungal pulmonary infection manifests as bronchitis or pneumonia. In the former, cough is the predominant symptom. Moreover, a cough that continues for more than 5 days is indicative of acute bronchitis [3]. Additionally, nearly half of patients with acute bronchitis produce sputum that may be clear, green or yellow, and occasionally streaked with blood. Patients will also report malaise, sore throat, headache, dyspnea, chest pain, hoarseness, and runny/stuffy nose.

Among the manifestations of pneumonia are fever, chills, malaise, cough, hemoptysis, worsening dyspnea, pleuritic chest pain, night sweats, and weight loss [4].

Pulmonary fungal infections may be accompanied by extrapulmonary manifestations. Associated manifestations, for example, will include arthritis, arthralgia, and skin conditions such as erythema nodosum and erythema multiforme. Moreover, fungal infections may disseminate to the brain, blood, bone marrow, kidneys, liver, spleen, sinuses, eye, and muscle.

Also, hypersensitivity reactions such as allergic bronchial asthma and allergic bronchopulmonary aspergillosis (ABPA) may develop secondary to Candida or Aspergillus or species [5]. There are numerous types of other allergic reactions as well.

Complications

Disseminated disease caused by opportunistic infections such as aspergillosis, candidal infection, and cryptococcal meningoencephalitis are common causes of death in immunocompromised patients [6].

Physical exam

Notable signs of acute bronchitis include tachypnea, wheezing, rhonchi, rales and prolonged expiration [7] [8].

In cases of pneumonia, persistent fever is one of the initial symptoms. Other vital signs changes include tachycardia and tachypnea. Further manifestations may include pleural rub, pericardial rub, consolidation, rales, and other adventitious sounds. Also, patients often exhibit signs of distress.

If skin and rheumatologic syndromes are present, then appropriate clinical findings will be observed. Furthermore, patients with meningitis will demonstrate nuchal rigidity and altered mental status.

• Malaise

  Patients will also report malaise, sore throat, headache, dyspnea, chest pain, hoarseness, and runny/stuffy nose. [symptoma.com]

  General symptoms associated with this form of aspergillosis include fever, night sweats, a cough that brings up sputum, fatigue, a general feeling of poor health (malaise), and unintended weight loss. [rarediseases.org]

  Symptomatic infection is associated with cough, chest pain, fevers, malaise, sputum production, and hemoptysis. [clinicaladvisor.com]

  A case report • A 71-year-old Chinese male was admitted with complaint of chronic cough and malaise for two months. He had been in Tucson, Arizona, USA, visiting for four months right before the symptoms occurred. [slideshare.net]

  Symptoms of Valley Fever Around 30%-35% of individuals develop flu-like symptoms, including a cough, fever, chills, and malaise that can get resolved more than two to six weeks without getting treated. [valley-fever.org]

• Lymphadenopathy

  Endemic mycoses may cause lymphadenopathy and obstruction of large airways through pressure effects. [patient.info]

  Radiographic findings include focal nodular or patchy infiltrates, and mediastinal/hilar lymphadenopathy. [clinicaladvisor.com]

  Right hilar and mediastinal lymphadenopathy was noted. Lung cancer was considered as the most likely diagnosis. Subsequent bronchoscopy and brush cytology were negative. [slideshare.net]

  There was no organomegaly or peripheral lymphadenopathy. On investigation, the blood haemoglobin concentration was 53 g/l, total leucocyte count 16.6 × 10 9 /l, and platelet count 28.0 × 10 9 /l. Peripheral blood smear revealed 90% myeloblasts. [pmj.bmj.com]

• Hypoxemia

  Most patients have hypoxemia and increased alveolar-arterial (A-a) oxygen gradient on presentation. CXR may be unremarkable in early mild disease and chest CT may be helpful in these cases. [clinicaladvisor.com]

• Pneumonia

  In cases of pneumonia, persistent fever is one of the initial symptoms. Other vital signs changes include tachycardia and tachypnea. [symptoma.com]

  Fungal pneumonia can be treated with antifungal drugs and sometimes by surgical debridement. Pneumonia Coccidioidomycosis [en.wikipedia.org]

  chlamydial pneumonia ( J16.0 ) gonorrheal pneumonia ( A54.84 ) histoplasmosis pneumonia ( B39.0- B39.2 ) measles pneumonia ( B05.2 ) nocardiosis pneumonia ( A43.0 ) pneumocystosis ( B59 ) pneumonia due to Pneumocystis carinii ( B59 ) pneumonia due [icd10data.com]

  The radiographic findings in aspergillus and mucoraceae pneumonia are also non-specific. [pmj.bmj.com]

  Pneumonia When Candida infects the lungs, it can cause pneumonia, resulting in several different symptoms. A fever is often one of the first symptoms. [livestrong.com]

• Cough

  In the former, cough is the predominant symptom. Moreover, a cough that continues for more than 5 days is indicative of acute bronchitis. [symptoma.com]

  Lung symptoms include fever, wheezing, and coughing. Patients may cough up blood or mucous plugs. Sinus symptoms include facial pressure, headache, blocked nose, yellow or green discharge from the nose, and cough. [dermnetnz.org]

  Symptoms are often similar to the symptoms of pneumonia, including difficulty breathing; wheezing; a dry, unproductive cough; and chest pain. [livestrong.com]

  The symptoms commonly include shortness of breath, wheezing, coughing, runny nose, and headaches. Fungal balls, or aspergilloma, can form when hyphal colonies collect in the lungs (Figure 4). [courses.lumenlearning.com]

  People may have no symptoms or may cough up blood or have a fever, chest pain, and difficulty breathing. If fungi spread to the liver or kidneys, these organs may malfunction. [merckmanuals.com]

• Hemoptysis

  In these nine patients, seven presented massive hemoptysis and all died of that; other two patients presented severe hemoptysis. [ncbi.nlm.nih.gov]

  Aspergillomas are often asymptomatic but may present with cough and rarely life threatening hemoptysis. [clinicaladvisor.com]

  Among the manifestations of pneumonia are fever, chills, malaise, cough, hemoptysis, worsening dyspnea, pleuritic chest pain, night sweats, and weight loss. Pulmonary fungal infections may be accompanied by extrapulmonary manifestations. [symptoma.com]

• Dyspnea

  Patients will also report malaise, sore throat, headache, dyspnea, chest pain, hoarseness, and runny/stuffy nose. [symptoma.com]

  Coughing that does not produce mucus; difficulty breathing, also called dyspnea; or abnormally fast breathing, known as tachypnea, are additional frequent symptoms of Candida pneumonia. [livestrong.com]

  PCP in HIV usually presents with an insidious onset of dry cough, progressive dyspnea, weight loss, and fever. Acute dyspnea and chest pain should raise suspicion for a pneumothorax. [clinicaladvisor.com]

  One of the following symptoms of lower respiratory tract infection: new sputum secretions, dyspnea, or hemoptysis; pleuritic chest pain; or physical finding of pleural rub in the background of host factor and microbiological criteria. [ejbronchology.eg.net]

  | N Engl J Med 2017; 377:2580 A 29-year-old man presented with 2 months of fever, cough, dyspnea, and weight loss. Biopsy of extensive cutaneous lesions revealed Talaromyces marneffei. [nejm.org]

• Chronic Cough

  Ogawa H, Fujimura M, Takeuchi Y, Makimura K (2009) Efficacy of itraconazole in the treatment of patients with chronic cough whose sputa yield basidiomycetous fungi-Fungus-associated chronic cough (FACC). [journals.plos.org]

  They can experience unintended weight loss, a chronic cough that produces mucus, the coughing up of blood, fatigue, and shortness of breath. Less often, fever or night sweats can occur. [rarediseases.org]

  A case report • A 71-year-old Chinese male was admitted with complaint of chronic cough and malaise for two months. He had been in Tucson, Arizona, USA, visiting for four months right before the symptoms occurred. [slideshare.net]

  Chronic cough, dyspnea, wheezes, and cyanosis were present in both groups. Chest pain and hemoptysis were present in a small percentage of both groups (11.6 vs. 8.3 and 6.2 vs. 5.2) in COPD patients with and without comorbidities, respectively. [ejbronchology.eg.net]

• Stroke

  If the central nervous system is involved, it can present with a stroke. Additional Forms of Aspergillosis Aspergillosis may occur as an isolated infection of individual areas such as the nail beds, eyes, skin, sinuses or ear canals. [rarediseases.org]

The workup of a pulmonary infection includes evaluation of the patient's medical history, risk factors, and exposures as well as any recent travel to regions of endemic fungal infection. Furthermore, the patient warrants a complete physical exam and diagnostic studies.

Laboratory tests

A complete blood count (CBC) with differential will reveal leukocytosis in immunocompetent patients with endemic infection whereas it shows leukopenia or neutropenia in those with an opportunistic infection. Moreover, eosinophilia is suggestive of aspergillosis [9].

To determine the etiology of the infection, cultures of sputum, blood, and bronchoalveolar lavage (BAL) fluid are obtained. Another important diagnostic technique is the microscopic analysis of respiratory secretions with specific stains and potassium hydroxide (KOH) preparation [2].

Depending on the pathogen, certain antigen detection studies with polymerase chain reaction (PCR) [10] and enzyme-linked immunosorbent assay (ELISA) [11] are available. Other nonculture methods include galactomannan assays for Aspergillus or Histoplasma [12] [13].

Imaging

Chest radiography in patients with a pulmonary fungal disease may demonstrate consolidation, nodules, and cavitation. Hilar or mediastinal adenopathy also develop in those with fungal infection [2].

Computed tomography (CT) scans are helpful in the assessment of pulmonary lesions found in immunocompromised individuals. Specifically, this imaging modality reveals the "halo sign'" in those with invasive aspergillosis [14].

Other

Procedures used in the diagnosis of pulmonary masses include fiberoptic bronchoscopy and percutaneous CT-guided fine-needle aspiration [15] [16].

• Pulmonary Infiltrate

  The usual causes of pulmonary infiltrates in patients with leukaemia are infection and haemorrhage. [pmj.bmj.com]

  CXR: May show patchy infiltration, nodules, consolidation, cavitation or pleural effusion. Pronounced mediastinal lymphadenopathy - some endemic fungal pneumonias. Miliary-pattern pulmonary infiltration in extensive disease. [patient.info]

  Development of new pulmonary infiltrates on chest radiograph. Any of the following new infiltrates on CT imaging: halo sign, air-crescent sign, or cavity within area of consolidation. [ejbronchology.eg.net]

  Despite treatment with antibiotics, a repeat imaging study performed 8 weeks later showed a persistent pulmonary infiltrate. [nejm.org]

  Surgical resection of pulmonary fungal lesions should be considered when infiltrates are closely approximating large vessels, and in the setting of severe hemoptysis. [cancertherapyadvisor.com]

Special attention for IPFI treatment should be prophylaxis, early management as well as sufficient and a whole course administration of effective broad-spectrum antifungal agents. [ncbi.nlm.nih.gov]

Selection criteria: Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people [cochrane.org]

treatment between 24 and 48 h, and 52 (33.1%) patients received antifungal treatment after 48 h. [doi.org]

[…] time and plan, to establish China's own optimal antifungal treatment options, are reduced in patients with severe fungal infection harm and increase the rate of successful treatment with evidence-based medical evidence. [clinicaltrials.gov]

Keywords Invasive fungal infection Pulmonary, hematologic disease Hemoptysis Antifungal treatment This is a preview of subscription content, log in to check access. [link.springer.com]

The prognosis of IPFI patients with massive hemoptysis is very poor. Special attention for IPFI treatment should be prophylaxis, early management as well as sufficient and a whole course administration of effective broad-spectrum antifungal agents. [ncbi.nlm.nih.gov]

Serology may be useful for diagnosis (and prognosis) of some mycotic diseases such as coccidioidomycosis, pythiosis, and lagenidiosis. [merckvetmanual.com]

The prognosis varies widely depending on the organism, adequacy of treatment, and the ability of the host to restore their immune system. [clinicaladvisor.com]

Hence early institution of antifungal therapy based primarily on clinical grounds is recommended. 9 Candida pneumonia is usually a part of disseminated candidiasis and has a poor prognosis. [pmj.bmj.com]

To determine the etiology of the infection, cultures of sputum, blood, and bronchoalveolar lavage (BAL) fluid are obtained. [symptoma.com]

Typical fungal etiologies include aspergillosis, mucormycosis, and fusariosis. [cancertherapyadvisor.com]

EW The most common presentation of a leukemia patient with a fungal infection is a neutropenic fever of unexplained etiology. Typically, patients who develop a neutropenic fever will initially begin treatment with broad-spectrum antibiotics. [hematologyandoncology.net]

Pulmonary infiltrates in patients receiving long-term glucocorticoid treatment: etiology, prognostic factors, and associated inflammatory response. Chest 2003; 123 :488–498. 26. Guinea J, Torres-Narbona M, Gijón P, Muñoz P, Pozo F, Peláez T et al. [ejbronchology.eg.net]

However, over the last decade, a number of uncommon filamentous fungi, such as Scedosporium, Fusarium, Penicillium, melanized moulds, and basidiomycetes, have emerged as etiological agents of well-characterized respiratory disorders. [journals.plos.org]

The following data was assessed: Epidemiology, laboratory and radiological features, microbiology, treatment and risk factors. Results : The medical sample consisted of 62 patients, 30 ICT and 32 ICP. [erj.ersjournals.com]

[…] populations Under-diagnosed and mistaken for tuberculosis Severe asthma with fungal sensitisation (SAFS) >6,500,000 350,000 – 489,000 asthma deaths ~50% related to SAFS Uncertain Total ~13,000,000 1,600,000 Probably a significant underestimate View all Epidemiological [gaffi.org]

Nosocomial acquisition of Candida albicans : an epidemiologic study. J. Infect. Dis. 168 : 195 -201. ↵ Weinstein, M. P., S. Mirrett, M. L. Wilson, L. G. Reimer, and L. B. Reller. 1994. [doi.org]

In epidemiological review of 929 patients with zygomycosis by Roden et al., the incidence of Mucor sinus infection was more common followed by pulmonary and cutaneous. [jtd.amegroups.com]

Author address: UZ Gasthuisberg Leuven, Belgium Abstract: A concerning trend in the epidemiology of pulmonary fungal infections, is the increasing incidence of patients in which traditional risk factors such as neutropenia are lacking. [aspergillus.org.uk]

Novel perspectives on mucormycosis: pathophysiology, presentation, and management. Clin Microbiol Rev. 2005;18:556-569. 16. Harris JR, Balajee SA, Park BJ. Pneumocystis jirovecii pneumonia: current knowledge and outstanding public health issues. [uspharmacist.com]

The present review addresses the epidemiology and pathophysiology of IPA in COPD patients. [erj.ersjournals.com]

Moreover, new pathophysiological associations hitherto unknown, such as fungal sensitization and ABPM in patients with chronic obstructive pulmonary disease (COPD), are unfolding [ 11, 12 ]. [journals.plos.org]

Optimal prevention strategies require additional study. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. [ncbi.nlm.nih.gov]

Centers for Disease Control and Prevention (June 12, 2015 updated.) Candidiasis. Available online at http://www.cdc.gov/fungal/diseases/candidiasis/index.html. Accessed August 27, 2016. [labtestsonline.it]

Centers for Disease Control and Prevention (December 4, 2015 updated.) Ringworm. Available online at http://www.cdc.gov/fungal/diseases/ringworm/index.html. Accessed August 27, 2016. [labtestsonline.org]

1. Lamoth F, Alexander BD. Nonmolecular methods for the diagnosis of respiratory fungal infections. Clin Lab Med. 2014; 34(2):315-336.
2. Limper AH. The changing spectrum of fungal infections in pulmonary and critical care practice: clinical approach to diagnosis. Proc Am Thorac Soc. 2010;7(3):163–168.
3. Wenzel RP, Fowler AA 3rd. Clinical practice. Acute bronchitis. N Engl J Med. 2006; 355(20):2125-2130.
4. Centers for Disease Control and Prevention (CDC). Increase in Coccidioidomycosis - California, 2000-2007. MMWR Morb Mortal Wkly Rep. 2009; 58(5):105-109.
5. Denning DW, Pashley C, Hartl D, et al. Fungal allergy in asthma–state of the art and research needs. ClinTransl Allergy. 2014;4:14.
6. Segal BH, Walsh TJ. Current approaches to diagnosis and treatment of invasive aspergillosis. Am J Respir Crit Care Med. 2006;173(7):707-717.
7. Mufson MA. Viral pharyngitis, laryngitis, croup and bronchitis. In: Goldman L, Bennett JC, eds. Cecil Textbook of medicine. 21st ed. Philadelphia: Saunders, 2000:1793–1794.
8. Knutson D, Braun C. Diagnosis and Management of Acute Bronchitis. Am Fam Physician. 2002;65(10):2039-2045.
9. Agarwal R, Gupta D, Aggarwal AN, et al. Clinical significance of hyperattenuating mucoid impaction in allergic bronchopulmonary aspergillosis: an analysis of 155 patients. Chest. 2007; 132(4): 1183–1190.
10. Wheat LJ. Antigen detection, serology, and molecular diagnosis of invasive mycoses in the immunocompromised host. Transpl Infect Dis. 2006;8(3):128–139.
11. Löffler J, Hebart H, Sepe S, Schumcher U, Klingebiel T, Einsele H. Detection of PCR-amplified fungal DNA by using a PCR-ELISA system. Med. Mycol. 1998;36(5):275-279.
12. Husain S, Paterson DL, Studer SM, et al. Aspergillus galactomannan antigen in the bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in lung transplant recipients. Transplantation. 2007;83(10):1330–1336.
13. Hage CA, Davis TE, Egan L, et al. Diagnosis of pulmonary histoplasmosis and blastomycosis by detection of antigen in bronchoalveolar lavage fluid using an improved second-generation enzyme-linked immunoassay. Respir Med. 2007;101(1):43–47.
14. Greene RE, Schlamm HT, Oestmann JW, et al. Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign. Clin Infect Dis. 2007; 44(3):373-379.
15. Shannon VR, Andersson BS, Lei X, Champlin RE, Kontoyiannis DP. The changing spectrum of fungal infections in pulmonary and critical care practice: clinical approach to diagnosis. Bone Marrow Transplant. 2010;45(4):647-655.
16. Nosari A, Anghilieri M, Carrafiello G, et al. Utility of percutaneous lung biopsy for diagnosing filamentous fungal infections in hematologic malignancies. Haematologica. 2003;88(12):1405-1409.