Allergic bronchopulmonary aspergillosis (ABPA) is one of the main forms of pulmonary disease caused by aspergillus fumigatus, perhaps the most important fungal pathogen in clinical practice, together with candida albicans [1] [2] [3]. It is primarily diagnosed in children and younger adults [4], and signs and symptoms stem from a hypersensitivity reaction induced by repeated inhalation of A. fumigatus conidia, after which both innate and adaptive immune mechanisms initiate an inflammatory reaction [1] [4] [5]. ABPA is diagnosed in up to 6% of patients suffering from chronic asthma and in almost 15% of individuals harboring a diagnosis of cystic fibrosis, suggesting that these two conditions are most important risk factors [5] [6]. In the majority of cases, clinical deterioration of preexisting pulmonary disease is the principal manifestation, with symptoms such as more pronounced cough, wheezing, increased sputum production, hemoptysis, dyspnea, chest pain and the appearance of exercise-induced asthma [2] [6]. Recurrent fever can also be reported [6]. In more severe cases, cyanosis, digital clubbing, and cor pulmonale can be present. However, patients often show minimal signs of the disease for a prolonged period of time, especially if neither asthma nor CF is present [6]. Moreover, without an adequate diagnosis and early initiation of therapy, the clinical course of ABPA is distinguished by repeated remission and exacerbation of symptoms, eventually leading to pulmonary fibrosis, bronchiectasis and chronic production of sputum [2] [3]. The importance of early recognition lies in the fact that pulmonary fibrosis has a poor long-term outcome and may progress to respiratory failure [2] [5].

• Fever

  The first indications of allergic bronchopulmonary aspergillosis are usually symptoms, such as wheezing, cough, and shortness of breath, and a mild fever. Symptoms tend to become progressively more severe, except for fever. [merck.com]

  Allergic bronchopulmonary aspergillosis (ABPA) is primarily a disease of patients with cystic fibrosis or asthma, who typically present with bronchial obstruction, fever, malaise, and expectoration of mucus plugs. [ncbi.nlm.nih.gov]

  Aspergillus fumigatus and Aspergillus niger, while less severe effects are caused by Aspergillus flavus and Aspergillus clavatus The signs and symptoms associated with Aspergillosis are cough with sputum and blood, breathing difficulties, wheezing, fever [dovemed.com]

  The first indications of allergic bronchopulmonary aspergillosis are usually symptoms such as wheezing, cough, and shortness of breath, and a mild fever. Symptoms tend to become progressively more severe, except for fever. [msdmanuals.com]

• Constitutional Symptom

  In this case report, we documented middle age male with known asthma case for many years with constitutional symptoms such as cough, fever, and shortness of breath diagnosed as TB and received anti-TB treatment for 4 weeks. [ncbi.nlm.nih.gov]

  Clinical presentation and diagnosis Patients frequently complain of constitutional symptoms such as fever, malaise, fatigue, and weight loss of 1–6 months' duration, in addition to chronic productive cough and haemoptysis, which varies from mild to severe [doi.org]

• Chills

  Possible Complications Health problems from the disease or treatment include: Amphotericin B can cause kidney damage and unpleasant side effects such as fever and chills Bronchiectasis (permanent scarring and enlargement of the small sacs in the lungs [mountsinai.org]

  If the disease progresses, symptoms may include: Coughing, sometimes accompanied by mucus or blood Wheezing Fever Chest pain Difficulty breathing Symptoms of invasive aspergillosis may include: Fever Chills Breathing difficulties, such as shortness of [my.clevelandclinic.org]

  Signs and symptoms depend on which organs are affected, but in general, invasive aspergillosis can cause: Fever and chills A cough that brings up blood (hemoptysis) Shortness of breath Chest or joint pain Headaches or eye symptoms Skin lesions Other types [mayoclinic.org]

• Cough

  The symptoms are similar to those of asthma: intermittent episodes of feeling unwell, coughing and wheezing. Some patients cough up brown-coloured plugs of mucus. The diagnosis can be made by chest X-ray along with sputum, skin and blood tests. [aspergillus.org.uk]

  […] as in asthmatics Severe attacks of Aspergillosis are caused by Aspergillus fumigatus and Aspergillus niger, while less severe effects are caused by Aspergillus flavus and Aspergillus clavatus The signs and symptoms associated with Aspergillosis are cough [dovemed.com]

  People may cough and wheeze, and they sometimes have fever or cough up flecks of blood. Doctors use chest x-rays, blood tests, and skin tests to make a diagnosis. Drugs used in the treatment of asthma, especially corticosteroids, are usually given. [merck.com]

  […] relieved by coughing up plugs or very thick mucous. [life-worldwide.org]

• Hemoptysis

  […] if pulmonary function is adequate Bronchial artery embolization may be used for life-threatening hemoptysis in patients unlikely to tolerate surgery or in patients with recurrent hemoptysis (eg, patients with CF in whom hemoptysis may be related to underlying [emedicine.medscape.com]

  The disease clinically manifests with poorly controlled asthma, hemoptysis, systemic manifestations like fever, anorexia and weight loss, fleeting pulmonary opacities and bronchiectasis. [ncbi.nlm.nih.gov]

  Hemoptysis — The coughing up of large amounts of blood. Hemoptysis can occur as a complication of ABPA. Hypersensitivity — An excessive response by the body to a foreign substance. [medical-dictionary.thefreedictionary.com]

• Pulmonary Disorder

  Differential Diagnosis Aspergillus hypersensitive bronchial asthma pulmonary tuberculosis in endemic areas community-acquired pneumonia (especially acute presentations) other inflammatory pulmonary disorders eg. eosinophilic pneumonia, bronchocentricgranulomatosis [slideshare.net]

  Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder that results from immune responses mounted against antigens of Aspergillus fumigatus, resulting in non-specific respiratory symptoms and structural lung damage. [ncbi.nlm.nih.gov]

• Productive Cough

  Here we report the case of a 13-year-old girl with ABPA who presented with productive cough, bronchiectasis and decline in lung function, and review the clinical features and treatment for pediatric ABPA. [ncbi.nlm.nih.gov]

  Symptoms and signs are those of asthma with the addition of productive cough and, occasionally, fever and anorexia. [msdmanuals.com]

  Learn about this topic in these articles: symptoms In aspergillosis allergic bronchopulmonary aspergillosis, seen especially in patients with chronic pulmonary diseases, include a chronic productive cough and purulent sputum occasionally tinged with blood [britannica.com]

• Chronic Productive Cough

  Learn about this topic in these articles: symptoms In aspergillosis allergic bronchopulmonary aspergillosis, seen especially in patients with chronic pulmonary diseases, include a chronic productive cough and purulent sputum occasionally tinged with blood [britannica.com]

  In chronic ABPA, the acute episodes are superimposed on a background of chronic cough and sputum production. [clinicaladvisor.com]

  Symptoms are nonspecific and usually mimic bronchopneumonia: fever unresponsive to antibiotics, cough, sputum production and dyspnoea. [doi.org]

The diagnosis of ABPA is not easy to attain in patients who develop nonspecific lung-related signs and symptoms, especially when pulmonary conditions, such as asthma and CF, are concomitantly present. A detailed patient history and a thorough physical examination (with an emphasis on pulmonary auscultation), however, are detrimental parts of the diagnostic workup, as they can identify recent exacerbation or the appearance of new lung-related symptoms. Moreover, many individuals already have some other allergic disorders (for eg. rhinitis, conjunctivitis, atopic dermatitis, etc.), which may be another clue toward ABPA as a differential diagnosis [4]. Because clinical findings are not specific for the diagnosis of ABPA, its recognition relies on the fulfillment of the following criteria [1] [2] [6] [7] [8]:

• History of asthma (considered to be one of the main prerequisites).
• Clinical deterioration of preexisting pulmonary symptoms (if patients suffer from asthma or CF).
• Immediate hypersensitivity to aspergillus spp. confirmed by a skin prick test.
• Elevated serum immunoglobulin (Ig) E levels (> 416 IU/mL or > 1000 ng/mL).
• Presence of IgE or IgG-specific antibodies to aspergillus spp.
• Peripheral blood eosinophilia confirmed on a complete blood count (CBC).
• Radiographic signs - Plain radiography, often employed as the initial imaging method, shows pulmonary infiltrates and consolidation (also termed non-homogenous opacities), as well as mucus plugs, lobar or segmental lung collapse and presence of fluid in the bronchi in the initial stages of the disease [4] [6]. Inflammation of the airways, often designated as "tramline" sign, is frequently visible in patients suffering from ABPA, whereas other notable radiographic features are edema of the bronchial wall, "toothpaste" shadows, and mucoid plugs causing "glover finger" opacities [4] [6]. Although plain radiography can be highly useful, high-resolution computed tomography (HRCT) is proven to be a superior method for evaluation of many pulmonary diseases, including ABPA, due to its ability to visualize lesions in more detail [1] [4] [5] [6]. For this reason, HRCT should be used whenever possible in patients with suspected ABPA.

• Skin Test Positive

  Diagnosis and Diagnostic Criteria Rosenberg-Patterson criteria Major criteria ( ARTEPICS ) A = Asthma R = Roentgenographic fleeting pulmonary opacities T = Skin test positive for Aspergillus(type I) E = Eosinophilia P = Precipitating Abs (IgG) in serum [slideshare.net]

  An immediate wheal-and-flare reaction should prompt measurement of serum IgE and Aspergillus precipitins because up to 25% of patients with asthma without ABPA may have a positive skin test. [merckmanuals.com]

  In fact, after analyzing both cases and controls, an 8 mm cutoff has been chosen to declare skin-test positivity. [journals.plos.org]

• Pulmonary Infiltrate

  Allergic bronchopulmonary aspergillosis (ABPA) is an allergic pulmonary disease comprising a complex hypersensitivity reaction to Aspergillus fumigatus. Clinical features of ABPA are wheezing, mucoid impaction, and pulmonary infiltrates. [ncbi.nlm.nih.gov]

  Examples include chronic eosinophilic pneumonia, Churg-Strauss syndrome, drug-induced pulmonary infiltrates, infection with a parasite, asthma with atelectasis, and lymphoma. [doi.org]

  A typical steroid dose is prednisone 0.5 mg/kg for approximately 2 weeks or until the pulmonary infiltrates clear. [asthma.partners.org]

• X-Ray Abnormal

  A chest x-ray may be abnormal and may look the same as the chest x-ray of someone with ‘pneumonia’ (but pneumonia is a different condition due to infection of the lung with other bugs). Often these x-ray changes can be ‘fleeting’ or come and go. [lungfoundation.com.au]

Oral corticosteroids are currently the treatment of choice for ABPA associated with bronchial asthma. They not only suppress the immune hyperfunction but are also anti-inflammatory. [clinicaltrials.gov]

[…] and Aspergillus niger, while less severe effects are caused by Aspergillus flavus and Aspergillus clavatus The signs and symptoms associated with Aspergillosis are cough with sputum and blood, breathing difficulties, wheezing, fever, and chest pain Treatment [dovemed.com]

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 [ncbi.nlm.nih.gov]

Conclusion Treatment Corticosteroid : drug of choice Itraconazole : adjunctive therapy [slideshare.net]

[…] and requires urgent medical attention; otherwise, it may become fatal Please find comprehensive information on Aspergillosis regarding definition, distribution, risk factors, causes, signs & symptoms, diagnosis, complications, treatment, prevention, prognosis [dovemed.com]

The fibrotic stage is an advanced stage of radiographic abnormalities with asthma, irreversible and partially reversible obstructive pulmonary function changes, and poor prognosis. [annals.org]

Outlook and prognosis Excellent prognosis and few symptoms if well controlled. Complication of bronchiectasis in asthma common and may be present at diagnosis. Usually centrally located and somewhat distinctive on CT scan. [life-worldwide.org]

Consensus Conference Proposed Diagnostic Criteria for ABPA in CF Classic diagnostic criteria Acute or subacute clinical deterioration not explained by another etiology total IgE > 1,000 IU/mL Immediate cutaneous reactivity to Aspergillus or presence of [slideshare.net]

Diagnostic Criteria Recommendations Evaluation of the Evidence Acute or subacute clinical deterioration (cough, wheeze, exercise intolerance, exercise-induced asthma, change in pulmonary function, or increased sputum production) not attributed to another etiology [cff.org]

Etiology ABPA is an immunologic disorder due to a predominant T-helper 2 lymphocyte response to Aspergillus fumigatus infection without tissue invasion. [orpha.net]

Ongoing controversies regarding etiology, diagnosis, treatment Diagnosis ABPA probably represents the extreme in a spectrum of A. fumigatus sensitive lung diseases in asthmatic and CF patients. [clinicaladvisor.com]

Areas addressed included fungal biology, immunopathogenesis, insights from animal models, diagnostic criteria, epidemiology, the use of new immunologic and genetic techniques in diagnosis, imaging modalities, pharmacology, and treatment approaches. [ncbi.nlm.nih.gov]

Outline Definition Epidemiology Pathogenesis Pathology Clinical feature Laboratory finding Diagnosis Management 3. [slideshare.net]

Reported prevalence, regional distribution, and patient characteristics.Scientific Advisory Group Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis. Chest 1999; 116: 639-646. [cfmedicine.com]

A European epidemiological study. Epidemiologic Registry of Cystic Fibrosis. Eur Respir J. 2000;16(3):464-71. [ Links ] 25. Laufer P, Fink JN, Bruns WT, Unger GF, Kalbfleisch JH, Greenberger PA, et al. [scielo.br]

The pathophysiologic mechanisms are mediated by a first and direct interaction of Aspergillus fumigatus (Af) antigens with airway epithelial cells, followed by an immunologic/allergic inflammatory response to Af antigens. [ncbi.nlm.nih.gov]

Allergic bronchopulmonary mycosis–pathophysiology, histology, diagnosis, and treatment. Asia Pacific Allergy. 2018 Jul 23;8(3). [physio-pedia.com]

"Pathophysiology and immunology of allergic bronchopulmonary aspergillosis". Medical Mycology. 43 (s1): 203–206. CiteSeerX 10.1.1.585.3463. doi:10.1080/13693780500052255. PMID 16110813. [wikipredia.net]

Pathophysiology For unclear reasons, colonization in these patients prompts vigorous antibody (IgE and IgG) and cell-mediated immune responses (type I, III, and IV hypersensitivity reactions ) to Aspergillus antigens, leading to frequent, recurrent asthma [merckmanuals.com]

Pathophysiology of ABPA. From Aspergillus adherence and penetration of the bronchial mucosa to the B and T cell response Allergy 2005: 60: 1004–1013 7. [slideshare.net]

The importance of recognizing ABPA relates to the improvement of patient symptoms, and delay in development or prevention of bronchiectasis, one manifestation of permanent lung damage in ABPA. [ncbi.nlm.nih.gov]

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