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    Allergic Bronchopulmonary Aspergillosis (ABPA)

    Allergic bronchopulmonary aspergillosis is a disease characterized by a hypersensitivity reaction to aspergillus fumigatus after its repeated inhalation and is most frequently encountered in patients suffering from asthma or cystic fibrosis (CF). The diagnosis is based on clinical, radiographic and microbiological criteria, but symptoms may not be apparent until advanced stages of the disease occur.

    The disease is related to the following process: infectious.

    Presentation

    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].

    Entire body system
    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]
    • Signs and symptoms depend on which organs are affected, but in general, invasive aspergillosis can cause: Fever and chills Cough that brings up blood-streaked sputum (hemoptysis) Severe bleeding from your lungs Shortness of breath Chest or joint pain[mayoclinic.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]
    Constitutional Symptom
    • […] all the criteria and there is no documented mucoid impaction on CT chest or bronchoscopy 2 Response Clinical improvement (resolution of constitutional symptoms, improvement in asthma control) Major radiological improvement* IgE decline by 25% of baseline[researchgate.net]
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  • respiratoric
    Chronic Cough
    • In the chronic stage, the symptoms are chronic cough, dyspnea, fatigue, anorexia, and weight loss.[hindawi.com]
    Chronic Productive Cough
    • Learn about this topic in these articles: symptoms Characteristic symptoms of allergic bronchopulmonary aspergillosis , seen especially in patients with chronic pulmonary diseases, include a chronic, productive cough and purulent sputum occasionally tinged[britannica.com]
    Cough
    • Along with a persistent cough, breathlessness, tiredness and weight loss, coughing up blood is a common symptom.[nhs.uk]
    • Aspergilloma is a benign condition that may not produce symptoms or may produce a mild cough only, but over time, the underlying condition can worsen and possibly cause: A cough that often brings up blood (hemoptysis), sometimes large amounts Wheezing[mayoclinic.org]
    • […] breath Kidney or liver failure Shock Bloody cough or massive bleeding from the lungs Allergic bronchopulmonary aspergillosis may cause: Coughing accompanied by mucus or blood Wheezing or worsening of asthma Fever Increased mucus or sputum secretions[my.clevelandclinic.org]
    • This leads to symptoms such as wheezing and coughing.[fairview.org]
    • Some patients cough up brown-coloured plugs of mucus.[aspergillus.org.uk]
    Hemoptysis
    • However, it may cause hemoptysis.[emedicine.medscape.com]
    • […] in patients thought to have insufficient pulmonary reserve to tolerate surgery or in patients with recurrent hemoptysis (eg, patients with CF in whom hemoptysis may be related to underlying bronchiectasis with or without aspergilloma). [11] Bronchial[emedicine.medscape.com]
    • Aspergilloma is a benign condition that may not produce symptoms or may produce a mild cough only, but over time, the underlying condition can worsen and possibly cause: A cough that often brings up blood (hemoptysis), sometimes large amounts Wheezing[mayoclinic.org]
    • Hemoptysis can occur as a complication of ABPA.[medical-dictionary.thefreedictionary.com]
    • Although affected individuals can occasionally be asymptomatic, most of them present with wheezing, bronchial hyperreactivity, hemoptysis, productive cough, low-grade fever, malaise, weight loss, and/or worsening symptoms of asthma and cystic fibrosis[orpha.net]
    Productive Cough
    • Learn about this topic in these articles: symptoms Characteristic symptoms of allergic bronchopulmonary aspergillosis , seen especially in patients with chronic pulmonary diseases, include a chronic, productive cough and purulent sputum occasionally tinged[britannica.com]
    • Symptoms and signs are those of asthma with the addition of productive cough and, occasionally, fever and anorexia.[msdmanuals.com]
    • Although affected individuals can occasionally be asymptomatic, most of them present with wheezing, bronchial hyperreactivity, hemoptysis, productive cough, low-grade fever, malaise, weight loss, and/or worsening symptoms of asthma and cystic fibrosis[orpha.net]
    • Exacerbations mimic the initial (acute) presentation, typically characterized by productive cough, fever, dyspnea, and pulmonary infiltrates, sometimes with chest pain or hemoptysis.[asthma.partners.org]
    • Dur ing ABPA exacerbations, patients are symptomati c with fever, wheezing, hemop tysis and productive cough.[researchgate.net]
    Pulmonary Disorder
    • Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus, manifesting with poorly controlled asthma, recurrent pulmonary infiltrates and bronchiectasis.[ncbi.nlm.nih.gov]
    • Definitionallergic pulmonary disorder caused by hypersensitivity to Aspergillusfumigatus1Occurs in asthma or cystic fibrosis2result of immune response to Aspergillus colonization of airway and poor clearance of mucus secretionssubsequent bronchiectasis[slideshare.net]
    • Summary Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus , manifesting with poorly controlled asthma, recurrent pulmonary infiltrates and bronchiectasis .[onlinelibrary.wiley.com]
    • Chronic pulmonary aspergillosis Chronic pulmonary aspergillosis (CPA) is a long-term infection that usually only affects people with an underlying lung condition, such as tuberculosis (TB) , chronic obstructive pulmonary disorder (COPD) or sarcoidosis[nhs.uk]
    Rales
    • Focal inspiratory rales suggestive of a pneumonia or area of bronchiectasis may raise one's suspicion and lead to chest radiography.[asthma.partners.org]
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  • Workup

    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.

    Test Results

    Pulmonary Function Test
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  • Laboratory

    Serum
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  • Microbiology
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  • Imaging

    X-ray
    Pulmonary Infiltrate
    • Allergic Bronchopulmonary Aspergillosis Case Example A 23-year-old man was evaluated for asthma and bilateral pulmonary infiltrates.[asthma.partners.org]
    • Episodic bronchospasm, expectoration of mucous plugs, and fleeting pulmonary infiltrates are common manifestations of the disease.[ingentaconnect.com]
    • It is characterized by pulmonary infiltrates, eosinophilia, elevated serum immunoglobulin e, and skin reactivity to aspergillus antigen.[icd10data.com]
    • Diagnostic criteria for ABPA include the presence of asthma,a history of pulmonary infiltrates, peripheral blood eosinophilia, immediate-type skin reactivity, serum precipitating antibodies toAspergillus-specific IgE and IgG and central (proximal) bronchiectasis[ucdenver.edu]
    • Allergic bronchopulmonary aspergillosis (ABPA) is an immunological pulmonary disorder caused by hypersensitivity to Aspergillus fumigatus, manifesting with poorly controlled asthma, recurrent pulmonary infiltrates and bronchiectasis.[ncbi.nlm.nih.gov]
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  • Treatment

    Prognosis

    Complications

    Asthma
    • Poorly-controlled asthma is a common finding, with a case series only finding 19% of ABPA patients with well-controlled asthma.[en.wikipedia.org]
    • Pennington, MD, Pulmonologist, Wake Forest School of Medicine Click here for Patient Education Asthma and Related Disorders Asthma Drug Treatment of Asthma Treatment of Acute Asthma Exacerbations Allergic Bronchopulmonary Aspergillosis (ABPA) Allergic[msdmanuals.com]
    • […] symptoms, as measured by the Asthma Control Test (ACT).[dovepress.com]
    • The corticosteroid-dependent asthma stage may have recurrent exacerbations of allergic bronchopulmonary aspergillosis and severe asthma.[annals.org]
    • Asthma Sensitivity to A fumigatus can occur in atopic patients with asthma or CF; like other allergens, A fumigatus can cause bronchospasm on exposure.[consultantlive.com]
    Bronchiectasis
    • Bronchiectasis alone may be present in patients with asthma not complicated by ABPA but it is uncommon for asthmatics withoutABPA to have severe forms of bronchiectasis involving multiple lobes.[ucdenver.edu]
    • For a discussion of the differential diagnosis of bronchiectasis please refer to the article bronchiectasis and more specifically central bronchiectasis .[radiopaedia.org]
    • (See "Treatment of allergic bronchopulmonary aspergillosis" and "Clinical manifestations and diagnosis of bronchiectasis in adults" and "Treatment of bronchiectasis in adults" .)[uptodate.com]
    • ABPA causes airway inflammation, leading to bronchiectasis—a condition marked by abnormal dilation of the airways.[en.wikipedia.org]
    • Bronchiectasis is usually caused by recurrent inflammation of the airway and is a diagnostic criterion of ABPA.[medical-dictionary.thefreedictionary.com]
    Eosinophilia
    • Eosinophilia is usually also present.[medical-dictionary.thefreedictionary.com]
    • Beware of other causes of blood eosinophilia such as drugs, Churg Strauss, Wegeners, worms and tropical eosinophilia (Peckham et al, 2001 ).[cfmedicine.com]
    • Peripheral blood eosinophilia is common.[asthma.partners.org]
    • Markers Laboratory findings include: elevated Aspergillus -specific IgE elevated precipitating IgG against Aspergillus peripheral eosinophilia positive skin test Plain radiograph Early in the disease chest x-rays will appear normal, or only demonstrate[radiopaedia.org]
    • If the patient has asthma, eosinophilia and a history of infiltrates then ABPA should be considered as possible and the other tests can be done to attempt to confirm.[physio-pedia.com]
    Extrinsic Allergic Alveolitis
    • Extrinsic allergic alveolitis .[patient.info]
    • Hypersensitivity Pneumonitis Hypersensitivity pneumonitis (HP) or extrinsic allergic alveolitis is caused by a variety of antigens, including bird droppings (Pigeon Breeder’s disease), murine urine proteins (Laboratory Worker’s lung), thermophilic moldy[hindawi.com]
    Pulmonary Eosinophilia
    • .: Corticosteroid treatment and prognosis in pulmonary eosinophilia .[link.springer.com]
    • Clinical Staging The spectrum of ABPA varies widely, from individuals with mild asthma and occasional episodes of pulmonary eosinophilia with no long-term sequelae, to patients with fibrosis, honey-comb lung, and respiratory failure.[hindawi.com]
    Recurrent Pneumonia
    • Other patients will be diagnosed in the process of evaluating severe, steroid-dependent asthma or recurrent pneumonias in an asthmatic patient.[asthma.partners.org]
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  • Etiology

    Epidemiology

    Sex distribution
    Age distribution

    Pathophysiology

    Prevention

    Summary

    Patient Information

    Self-assessment

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    References

    1. Agarwal R, Chakrabarti A, Shah A, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy. 2013;43(8):850-873.
    2. Greenberger PA, Bush RK, Demain JG, Luong A, Slavin RG, Knutsen AP. Allergic Bronchopulmonary Aspergillosis. J Allergy Clin Immunol Pract. 2014;2(6):703-708.
    3. Mandell GL, Bennett JE, Dolin R. Mandel, Douglas and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, Pennsylvania: Churchill Livingstone; 2015.
    4. Tillie-Leblond I, Tonnel AB. Allergic bronchopulmonary aspergillosis. Allergy. 2005;60(8):1004-1013.
    5. Knutsen AP, Slavin RG. Allergic Bronchopulmonary Aspergillosis in Asthma and Cystic Fibrosis. Clin Dev Immunol. 2011;2011:843763.
    6. Shah A, Panjabi C. Allergic Bronchopulmonary Aspergillosis: A Perplexing Clinical Entity. Allergy Asthma Immunol Res. 2016;8(4):282-297.
    7. Agarwal R, Gupta D, Aggarwal AN, et al. Clinical significance of decline in serum IgE levels in allergic bronchopulmonary aspergillosis. Respir Med. 2010;104(2):204-210.
    8. Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology. Seventh edition. Philadelphia: Elsevier/Saunders; 2013.

    • A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis - DA Stevens, HJ Schwartz, JY Lee - England Journal of , 2000 - Mass Medical Soc
    • Allergic bronchopulmonary aspergillosis - RG Slavin, CC Gottlieb, LV Avioli - Archives of internal medicine, 1986 - Am Med Assoc
    • A review of non-cystic fibrosis pediatric bronchiectasis - EJ Boren, SS Teuber, ME Gershwin - Clinical Reviews in Allergy and , 2008 - Springer
    • In the collagen region of SP-A2 with increased levels of total IgE antibodies and eosinophilia in patients with allergic bronchopulmonary aspergillosis - S Saxena, T Madan, A Shah, K Muralidhar - Journal of allergy and , 2003 - Elsevier
    • A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis - DA Stevens, HJ Schwartz, JY Lee - England Journal of , 2000 - Mass Medical Soc
    • A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis - DA Stevens, HJ Schwartz, JY Lee - England Journal of , 2000 - Mass Medical Soc
    • Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis - AP Knutsen, RG Slavin - Clinical Reviews in Allergy and Immunology, 1991 - Springer
    • A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis - DA Stevens, HJ Schwartz, JY Lee - England Journal of , 2000 - Mass Medical Soc
    • Allergic bronchopulmonary aspergillosis - BA Cockrill, MD, CA Hales, MD - Annual review of medicine, 1999 - annualreviews.org
    • Adjunctive therapy of allergic bronchopulmonary aspergillosis with itraconazole. - DW Denning, JE Van Wye, NJ Lewiston - , 1991 - chestjournal.chestpubs.org
    • Allergic bronchopulmonary aspergillosis - I Tillie‐Leblond, AB Tonnel - Allergy, 2005 - Wiley Online Library
    • A practical workup for eosinophilia - ML Brigden - Postgraduate medicine, 1999 - postgradmed.org
    • A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis - DA Stevens, HJ Schwartz, JY Lee - England Journal of , 2000 - Mass Medical Soc
    • A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis - DA Stevens, HJ Schwartz, JY Lee - England Journal of , 2000 - Mass Medical Soc
    • In the collagen region of SP-A2 with increased levels of total IgE antibodies and eosinophilia in patients with allergic bronchopulmonary aspergillosis - S Saxena, T Madan, A Shah, K Muralidhar - Journal of allergy and , 2003 - Elsevier
    • Fumigatus allergens in A fumigatus–sensitized asthmatic subjects allows diagnostic separation of allergic bronchopulmonary aspergillosis from fungal - S Hemmann, G Menz, C Ismail, K Blaser - Journal of allergy and , 1999 - Elsevier
    • Adjunctive therapy of allergic bronchopulmonary aspergillosis with itraconazole. - DW Denning, JE Van Wye, NJ Lewiston - , 1991 - chestjournal.chestpubs.org
    • Allergic bronchopulmonary aspergillosis - PA Greenberger - Journal of Allergy and Clinical Immunology, 2002 - Elsevier
    • Allergic bronchopulmonary aspergillosis in cystic fibrosis—state of the art: Cystic Fibrosis Foundation Consensus Conference - DA Stevens, RB Moss, VP Kurup - Clinical Infectious , 2003 - cid.oxfordjournals.org
    • A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis - DA Stevens, HJ Schwartz, JY Lee - England Journal of , 2000 - Mass Medical Soc
    • Adjunctive therapy of allergic bronchopulmonary aspergillosis with itraconazole. - DW Denning, JE Van Wye, NJ Lewiston - , 1991 - chestjournal.chestpubs.org
    • A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis - DA Stevens, HJ Schwartz, JY Lee - England Journal of , 2000 - Mass Medical Soc
    • Adjunctive therapy of allergic bronchopulmonary aspergillosis with itraconazole. - DW Denning, JE Van Wye, NJ Lewiston - , 1991 - chestjournal.chestpubs.org
    • Allergic bronchopulmonary aspergillosis with low serum immunoglobulin E - RH Schwartz, GE Hollick - Journal of Allergy and Clinical Immunology, 1981 - Elsevier
    • Adjunctive therapy of allergic bronchopulmonary aspergillosis with itraconazole. - DW Denning, JE Van Wye, NJ Lewiston - , 1991 - chestjournal.chestpubs.org

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