Trichophyton Asthma
2009; Elsevier BV; Volume: 135; Issue: 4 Linguagem: Inglês
10.1378/chest.09-0114
ISSN1931-3543
AutoresThomas A.E. Platts‐Mills, Judith A. Woodfolk,
Tópico(s)Respiratory and Cough-Related Research
ResumoIn the current issue of CHEST (see page 898), Matsuoka et al1Matsuoka H Niimi A Matsumoto H et al.Specific IgE response to trichophyton and asthma severity.Chest. 2009; 135: 898-903Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar report on a strong association between sensitization to proteins from the fungus Trichophyton and the severity of asthma. Their report opens up an old controversy. In the 1930s, Cooke2Cooke R Allergy in theory and practice. WB Saunders, New York, NY1947: 130-159Google Scholar and others often referred to asthma presenting in adults as “infectious” rather than “intrinsic.” At that time, both bacterial and fungal infections were thought to be relevant to the occurrence of severe asthma in adults. Wise and Sulzberger3Wise F Sulzberger M Urticaria and hay fever due to Trichophyton (Epidermophyton interdigital).JAMA. 1930; : 1504-1508Crossref Scopus (28) Google Scholar argued further that onychomycosis was an important cause of sensitization associated with urticaria, sinus disease, or asthma. However, when Rackemann4Rackemann F A working classification of asthma.Am J Med. 1947; : 601Abstract Full Text PDF PubMed Scopus (186) Google Scholar described intrinsic asthma in 1948, the term was taken to be synonymous with “idiopathic” asthma. Subsequent to those conflicting views, many asthma specialists became nihilistic about the investigation of specific causes of asthma in adults. Despite this, there are now several well-recognized forms of adult asthma for which specific treatments are recommended. These include Samters triad and allergic bronchopulmonary aspergillosis (ABPA), as well as perennial asthma in patients with sensitization to indoor allergens.5Stevenson DD Simon RA Selection of patients for aspirin desensitization treatment.J Allergy Clin Immunol. 2006; 118: 801-804Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar, 6Stevens DA Schwartz HJ Lee JY et al.A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis.N Engl J Med. 2000; 342: 756-762Crossref PubMed Scopus (450) Google Scholar Vocal cord dysfunction should also be included among those forms of asthma with an etiologic basis because, though the mechanism of obstruction is very different, this condition is often misdiagnosed and treated inappropriately with oral steroids. Collectively, an important and unifying feature is that each of these types of asthma can benefit from different treatments. There are two other syndromes related to fungal sensitization that are less well recognized, but important to identify in individual cases. These are the various forms of allergic bronchopulmonary mycosis (ABPM) and “Trichophyton asthma.”7Greenberger PA Allergic bronchopulmonary aspergillosis.in: Adkinson Jr, NF Yunginger JW Busse WW Middleton's allergy: principles and practice. 6th ed. Mosby, Philadelphia, PA2003: 1353-1371Google Scholar, 8Ward Jr, GW Karlsson G Rose G et al.Trichophyton asthma: sensitisation of bronchi and upper airways to dermatophyte antigen.Lancet. 1989; 1: 859-862Abstract PubMed Scopus (99) Google Scholar In cases of ABPM, many different fungi can be present in the lungs including Curvularia, Drechslera, or Candida.7Greenberger PA Allergic bronchopulmonary aspergillosis.in: Adkinson Jr, NF Yunginger JW Busse WW Middleton's allergy: principles and practice. 6th ed. Mosby, Philadelphia, PA2003: 1353-1371Google Scholar The condition has symptoms in common with ABPA, and individual cases have been reported to respond to antifungal treatment. In relation to Trichophyton, we have published extensively on the sensitization to Trichophyton proteins in patients with severe asthma. These articles have included evidence that both the lungs and nose can be specifically sensitized although this fungus only colonizes the nails and skin8Ward Jr, GW Karlsson G Rose G et al.Trichophyton asthma: sensitisation of bronchi and upper airways to dermatophyte antigen.Lancet. 1989; 1: 859-862Abstract PubMed Scopus (99) Google Scholar; elucidation of key proteins that give rise to sensitization9Woodfolk JA Wheatley LM Piyasena RV et al.Trichophyton antigens associated with IgE antibodies and delayed type hypersensitivity: sequence homology to two families of serine proteinases.J Biol Chem. 1998; 273: 29489-29496Crossref PubMed Scopus (90) Google Scholar; and improvement of asthma in sensitized patients who received specific antifungal treatment in a controlled trial.1Matsuoka H Niimi A Matsumoto H et al.Specific IgE response to trichophyton and asthma severity.Chest. 2009; 135: 898-903Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 10Ward Jr, GW Woodfolk JA Hayden ML et al.Treatment of late-onset asthma with fluconazole.J Allergy Clin Immunol. 1999; 104: 541-546Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar The phenomenon of Trichophyton asthma has been confirmed in work from several countries including Venezuela, Turkey, and, now, Japan.1Matsuoka H Niimi A Matsumoto H et al.Specific IgE response to trichophyton and asthma severity.Chest. 2009; 135: 898-903Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 11Mungan D Bavbek S Peksari V et al.Trichophyton sensitivity in allergic and nonallergic asthma.Allergy. 2001; 56: 558-562Crossref PubMed Scopus (25) Google Scholar However, the clinical entity is not widely recognized, for several possible reasons. First, the condition is not very common; second, it generally requires intradermal skin tests to demonstrate sensitization, owing to the low quality of fungal extracts; and third, because physicians are surprisingly reluctant to prescribe systemic antifungal treatment. The article1Matsuoka H Niimi A Matsumoto H et al.Specific IgE response to trichophyton and asthma severity.Chest. 2009; 135: 898-903Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar in the current issue of CHEST reports on Trichophyton sensitization among a large cohort of patients with asthma presenting to a specialist clinic in Japan. Key findings are the strong association with the severity of asthma and the establishment of sensitization using serum radioallergosorbent assays for IgE antibodies to Trichophyton. When the significance of fungal colonization was first recognized, treatment posed a problem because there were no effective oral antifungal agents.3Wise F Sulzberger M Urticaria and hay fever due to Trichophyton (Epidermophyton interdigital).JAMA. 1930; : 1504-1508Crossref Scopus (28) Google Scholar As recently as 25 years ago, the situation was still not simple because the antifungal agents available, such as griseofulvin, ketoconazole, and amphoteracin B, had severe side effects. The situation has changed dramatically with the availability of less toxic antifungal agents (eg, fluconazole, itraconazole, and terbinafine). Both fluconazole and itraconazole have been used in successful controlled trials in patients with asthma.6Stevens DA Schwartz HJ Lee JY et al.A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis.N Engl J Med. 2000; 342: 756-762Crossref PubMed Scopus (450) Google Scholar, 10Ward Jr, GW Woodfolk JA Hayden ML et al.Treatment of late-onset asthma with fluconazole.J Allergy Clin Immunol. 1999; 104: 541-546Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar Most recently, Denning et al12Denning DW O'Driscoll BR Powell G et al.Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: the fungal asthma sensitization trial (fast) study.Am J Respir Crit Care Med. 2009; 179: 11-18Crossref PubMed Scopus (299) Google Scholar from Manchester, UK, reported a successful controlled trial of itraconazole therapy in patients with severe asthma and fungal sensitization. While the results were impressive, we think it is better to define the specific fungal organism involved and, if possible, treat the fungus specifically. In all patients with uncontrolled asthma who are sensitized to fungal antigens and have evidence of colonization, we would recommend the consideration of antifungal treatment. However, where possible the fungal organism in the lungs or on the feet should be identified. Though this may be challenging owing to the wide range of organisms that can colonize these sites. There is increasing evidence6Stevens DA Schwartz HJ Lee JY et al.A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis.N Engl J Med. 2000; 342: 756-762Crossref PubMed Scopus (450) Google Scholar, 13Hope WW Billaud EM Lestner J et al.Therapeutic drug monitoring for triazoles.Curr Opin Infect Dis. 2008; 21: 580-586Crossref PubMed Scopus (130) Google Scholar in favor of identifying the sensitivity in order to optimize antifungal treatment. We would particularly argue in favor of specifically identifying organisms in the lungs of patients with atypical ABPA or ABPM that may require bronchoscopy.6Stevens DA Schwartz HJ Lee JY et al.A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis.N Engl J Med. 2000; 342: 756-762Crossref PubMed Scopus (450) Google Scholar, 7Greenberger PA Allergic bronchopulmonary aspergillosis.in: Adkinson Jr, NF Yunginger JW Busse WW Middleton's allergy: principles and practice. 6th ed. Mosby, Philadelphia, PA2003: 1353-1371Google Scholar The important implication of recent developments is that asthma in adults that does not respond to first-line treatment should be investigated (Table 1). This investigation should include not only such routine investigations as lung function, sinus CT scanning, sensitization to common inhalant allergens, and evaluation of evidence for ABPA, but should also include an evaluation for evidence of colonization with a range of fungi including Alternaria, Candida, and Trichophyton as well as Aspergillus species.7Greenberger PA Allergic bronchopulmonary aspergillosis.in: Adkinson Jr, NF Yunginger JW Busse WW Middleton's allergy: principles and practice. 6th ed. Mosby, Philadelphia, PA2003: 1353-1371Google Scholar, 10Ward Jr, GW Woodfolk JA Hayden ML et al.Treatment of late-onset asthma with fluconazole.J Allergy Clin Immunol. 1999; 104: 541-546Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 12Denning DW O'Driscoll BR Powell G et al.Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: the fungal asthma sensitization trial (fast) study.Am J Respir Crit Care Med. 2009; 179: 11-18Crossref PubMed Scopus (299) Google Scholar It is important not to define patients as being steroid dependent or uncontrolled without excluding the causes that do respond to specific treatment.Table 1Fungal Colonization and Other Treatable Factors Related to Severity of Asthma*SyndromeTreatmentAspirin sensitivity and nasal polyps (Samters triad)Aspirin desensitizationVocal cord dysfunctionSpeech therapy or nebulized cromolynSensitization to indoor allergens and perennial exposureAllergen avoidance and/or immunotherapyABPAItraconazole of voreconazoleABPMRelevant antifungal treatmentTrichophyton asthmaFluconazole or itraconazole Open table in a new tab
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