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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 34  |  Issue : 2  |  Page : 98-102

Clinical significance of fungal sensitization in bronchial asthma: A prospective cross-sectional study at a tertiary care center


Department of Respiratory Medicine, Institute of Respiratory Diseases, SMS Medical College, Jaipur, Rajasthan, India

Date of Submission10-Feb-2020
Date of Acceptance10-Jun-2020
Date of Web Publication20-Nov-2020

Correspondence Address:
Dr. Jitendra Kumar Sharma
B-82, Subhash Nagar, Shastri Nagar, Jaipur - 302 016, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijaai.ijaai_6_20

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  Abstract 


INTRODUCTION: The link between fungi and asthma has been extensively investigated. However, the role of fungal allergens as the primary extrinsic factor leading to asthma severity has been incompletely explored. An all-new variant of asthma has been described recently which has been named severe asthma with fungal sensitisation (SAFS). It is characterised by the presence of severe asthma and are sensitized to one or more fungi but have normal or slightly elevated IgE concentration. In this study ALQ test and spirometry was done to assess the severity of asthma. ALQ test is a simple self administered questionnaire, designed to help individuals with breathing problems to determine if they have asthma or for those already diagnosed with asthma if their asthma is under control.
METHODS: A prospective observational study was done over a period of 6 months. Name, age, and demographic details collected from all bronchial asthma patients. Using SPT, the sensitization status to fungus was identified in clinically diagnosed bronchial asthma cases and asthma Severity with fungal sensitisation was analysed on the basis of asthma life quality test questionnaire and spirometry.
RESULTS: Out of hundred patients studied 60 of the patients were male. Mean duration of asthma was 5years. 40 patients were positive for fungal sensitization by SPT. The most common fungus was Curvularia Lulata followed by aspergillus. 30 patients were positive for aspergillus fungus (ALQ score > 16.5 and mean FEV1 was 28±2) as compared to the 10 patients who were positive for other than aspergillus fungus( ALQ score <16.5 and mean was FEV1 65 ±2 ) severe asthma. Fungal sensitization was found to be significantly associated with uncontrolled asthma. 75% of fungal sensitized patients had uncontrolled asthma as compared to 5% of the non fungal sensitized patients.
CONCLUSION: There was high prevalence of sensitization to all fungal allergens. Among all the fungal allergens, aspergillus sensitization is most commonly associated with severe asthma.

Keywords: Asthma life quality, Aspergillus, severe asthma with fungal sensitizations


How to cite this article:
Sharma JK, Jain S, Joshi V, Khippal N. Clinical significance of fungal sensitization in bronchial asthma: A prospective cross-sectional study at a tertiary care center. Indian J Allergy Asthma Immunol 2020;34:98-102

How to cite this URL:
Sharma JK, Jain S, Joshi V, Khippal N. Clinical significance of fungal sensitization in bronchial asthma: A prospective cross-sectional study at a tertiary care center. Indian J Allergy Asthma Immunol [serial online] 2020 [cited 2020 Nov 25];34:98-102. Available from: https://www.ijaai.in/text.asp?2020/34/2/98/300926




  Introduction Top


In today's time, asthma is termed to be a heterogeneous disease with varied clinical phenotypes. Each phenotype helps to illustrate one or more than one molecular endotype amenable to therapeutic intervention. In terms of allergic asthma, there remains a common asthma phenotype; much of the conflicting results persist and specifically remain in the role of allergen sensitization that determines the severity of the prognosis of the disease in asthma.[1] Across the varied types of allergens present around in the environment, the most commonly associated allergen is fungal sensitization that is associated with increased levels, resulting in severity in asthma. Increased severity results in the evidence of increased hospitalization for the exacerbations of the poorer lung functions. The symptom of the severity associated with asthma resulting in fungal sensitization has certainly been coined up with the characters in the presence of severe asthma, fungal sensitization, as well as the exclusion of the allergic bronchopulmonary aspergillosis. Studies focused on fungal sensitization in asthmatics tend to be heterogeneous and might have the inclusion of different asthma severities, helping in analyzing the conclusions at specified levels difficult to interpret. The subtype of the severe asthma is observed to be clinically recognized. Howsoever, data to support its true prevalence and treatment outcome still remain undefined in specificity.[2] Focusing on studies related to fungal sensitisation in asthmatics has to be included in different asthma patients with different stages of severity. In some cases, the data remain lacking in patients with severe asthma, thus affecting the hypothesis by undocumented fungal sensitization in such cases. The current literature focuses on the population with the consequent scantiness found in the literature based on allergen sensitization in the severe asthma population, mostly in the Asian belt. The allergen sensitization is more likely to be found in the eastern regions, as to be indifferent from other regions of the world due to a complicated interaction between the genetics and the environment helping in determining the individual's sensitization state. The prevalance of the sensitizagion includes Aspergillus Species and its assosciation was found in population having severe asthma and symptoms of asthma related to the fungal sensitization.[3] The relationship among the specific allergen sensitization and asthma severity is still unclear. This study aims to perform a detailed research on the prevalence of specific allergen sensitization criteria of patterns and investigate the association with the outcomes in severe asthma with specific allergen bodies such as Aspergillus fungus. Tests such as the Asthma Life Quality (ALQ) test and spirometry as well as some skin tests are performed to know the actual reason behind the severity of asthma. Breathing problems leading to bronchial symptoms are also the major prospects to have a glance on in this study. Various aspects of the severity of asthma are tried to be covered in this study to know in more depth about asthma severity and allied reasons, symptoms, and diagnostic measures as well.[4] Breathlessness and dry cough are some of the basic symptoms of bronchitis resulting in acute and severe asthma. Severe asthma with fungal sensitization (SAFS) caused due to fungal infection and slightly elevated IgE concentrations results in severity found in asthma.[5] The diagnosis of asthma was done on the basis of a history of episodic wheeze and dyspnea and clinical examination and supported by spirometry.


  Materials and Methods Top


This prospective observational study was conducted over a period of 6 months in the Institute of Respiratory Diseases, SMS Medical College, Jaipur. Name, age, and demographic details were collected from all bronchial asthma patients. Using skin prick test (SPT), the sensitization status to fungus was identified in clinically diagnosed bronchial asthma cases, and asthma severity with fungal sensitization was analyzed on the basis of ALQ test questionnaire and spirometry.[6] Demographic characteristics inclusive of age, ethnicity, the age of asthma onset, gender, the presence of allergic rhinitis, the family history of asthma, bronchial hyperresponsiveness, the status of smoking, and body mass index (BMI) are all need to be taken into consideration while judging the parameter that leads to severe asthma. Indicators of uncontrolled asthma, medications to be prescribed, health records, and clinical investigations needed to be done to judge the severity of asthma on the basis of the asthma detection tests and symptoms were observed.

Inclusion criteria for case population

Patients with newly diagnosed or known case of asthma.

Exclusion criteria for case population

This is the most crucial step in the diagnosis of SAFS. Patients with underlying cardiac diseases or chronic obstructive pulmonary disease and patients consistently unable to complete pulmonary function test.

Statistical analysis

The continuous variables were represented by means of the standard deviation or with the help of median (interquartile range), and comparison between the groups was performed using the independent t-tests and the Mann–Whitney U-test, from normal to nonnormal datasets. Comparisons were performed using the Pearson's and Fisher's exact test. Multivariate logistical regression was performed to estimate the odds ratios for the association between allergen sensitization and indicators that controlled asthma. Spirometry test, ALQ test, skin tests, etc., were performed to know the criteria for SAFS. Asthma control test scores were recorded at the baseline as as well, taking into account, the potential confounding factors such as ethnicity, gender, BMI, smoking history, and all the other allied allergen levels present such as Aspergillus and other fungus detection associated with asthma. Furthermore, multivariate logistical regression was performed to estimate adjusted odds ratios. All the data were assessed with the Statistical Package for the Social Sciences with the help of analysis, and the P values were considered to be statistically significant.


  Results Top


As per the results, the majority of the patients were males, and mean age of all the patients was 42.4 years. As shown in [Figure 1] preliminary investigation showed that majority of as shown in [Figure 2]. Most of the females were homemaker as compared to most of male patients who were farmer by occupation as shown in [Figure 3] the patients were suffering from asthma from the last 5 years and had symptoms of a dry cough and dyspnea. Patients as shown in [Figure 4] complained that the symptoms get aggravated in winters, especially in morning hours. Forty patients were positive for fungal sensitization by SPT. The most common cause for this was Curvularia lunata as shown in [Figure 5] followed by Aspergillus as shown in [Figure 6]. The results showed that the mean forced expiratory volume in 1 s was lower (28 ± 2) for Aspergillus fungus as compared to other fungus (65 ± 2) as shown in [Table 1]. Finally, statistical analysis showed that there was a statistically significant association between fungal sensitization and uncontrolled asthma (P < 0.05) as 75% of fungal sensitized patients had uncontrolled asthma as compared to 5% of the nonfungal sensitized patients as shown in [Figure 7].
Figure 1: Out of the study population most of the patients were male with a male female ratio of 3:2

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Figure 2: Most of the cases studied were falling in the age range of 30-60 years with a mean age of 42.4

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Figure 3: Most of the females were homemaker as compared to most of male patients who were farmer by occupation

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Figure 4: Duration of Asthma in the range of 5 to 10 years showed more positive SPT test results

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Figure 5: Fungal sensitisation by SPT showed 40% positive cases

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Figure 6: Out of 40% SPT positive cases, maximum were that of Aspergillus group accounting for 30%

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Table 1: Mean FEV1 was lower for Aspergillus Fungus as compared to other Fungus

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Figure 7: Pie Chart showing Disease caused in Aspergillus Group, Out of which Maximum was SAFS seen In 20 Patients, ABPA And Mild asthma Was seen in 5 Patients Each.

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  Discussion Top


According to the study conducted on the severity of asthma named as “Severe asthma and fungi: current evidence” conducted by Agarwal and Gupta, the Medical Mycology, iit was stated that bronchial asthma is termed to be an inflammatory disease of the medium airways that may be worsened due to the numerous extrinsic factors.[7] The overwhelming evidence of the fungal sensitization in cases of asthma is seen. Hence, the diagnosis of fungal sensitization can be done with skin testing with antigens from fungi. There is a strong association amidst the fungal sensitization and the severity found in asthma. Aspergillus seems to be the strongest candidate with Aspergillus-sensitive asthma and allergic bronchopulmonary aspergillosis.

According to the study, “Allergic bronchopulmonary aspergillosis: A perplexing clinical entity,” it was found that in susceptible individuals, inhalation of Aspergillus spores can affect the respiratory tract in most of the ways. The spores get trapped in the viscid sputum of the asthmatic patients which trigger the cascade of inflammatory reactions. Imaging plays a compelling role in the diagnosis and monitoring of the disease. Demonstration of the elevated serum IgE levels and Aspergillus plays a vital role in the diagnosis of the fungal elements in the severity of the asthma.[8]

In support to the above studies through the current study, it was found that Aspergillus fungus was found associated with the asthmatic individuals.[9] Aspergillosis of the respiratory tract had diverse manifestations that range from hypersensitivity disorders to rapd invasive disseminated form hypersensitivity disorders to be displayed rapidly in the invasive disseminated criteria. Furthermore, there is a growing body of evidence to suggest the significance of the degree of airway colonization in patients sensitized to Aspergillus fumigatus, however, related to the allergic manifestations. Fungatus polymerase chain reaction, a more sensitive method such as spirometry and skin tests as well, is performed to know asthma's severity and treatment and diagnosis for the same. Aspergillus SPT and the IgE levels help in the measurement of severity and allergen sensitization of asthma.[10]

A runny nose, sneezing and hay fever-like symptoms are the significant nasal symptoms. Most of them are highly dependent on high-dose inhaled corticosteroids, with intermittent courses of oral steroids required for exacerbations and continuous oral steroids. Patients with SAFS are based on multiple medications.[11] Antifungal therapy with Itraconzole is beneficial in treating major effect of pulmonary and nasal symptoms. Although the clinical criteria of Aspergillus associated with respiratory disorders usually remain the mutually exclusive, immunopathologic responses may lead to the coexistence of different forms. The spores of this ubiquitous mould are dispersed by wind in the atmosphere and inhalation is the primary route of access and causes sensitisation in the patients of Asthma to imcrease the severity of the disease.[11] The occurence of aspergillus related hypersensitivity and respiratory disorder are seen in patients with SAFS.[12]

Fungi can be linked to the severity of asthma in many ways such as inhalation of fungal spores, through fungal sensitization (defined as the presence of immediate cutaneous hyperreactivity to fungal antigen or increase in specific IgE antibodies to a particular fungus) or through causation of allergic bronchopulmonary mycosis, and a severe degree of fungal sensitization with resultant irreversible bronchopulmonary damage.[13] In the recently published European Community Respiratory Health Survey, the frequency of sensitization to Alternaria or Cladosporium, or both, was a powerful risk factor for severe asthma in adults.[14] Previous studies have shown that exposure to environmental fungi increased the risk of death from asthma [15] and also acute attacks of asthma requiring intensive care unit admission.


  Conclusion Top


High allergen, mostly Aspergillus sensitization, was observed to result in severe asthma. Aspergillus sensitization was associated with frequent exacerbations and with greater corticosteroid requirements. Improved understanding of asthma severity with fungal sensitization is a must. In this study, there was a high prevalence of sensitization to all fungal allergens. Among all the fungal allergens, Aspergillus sensitization is most commonly associated with severe asthma.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Moore WC, Meyers DA, Wenzel SE, et al. Identification of asthma phenotypes using cluster analysis in the severe asthma research program. Am J Respir Crit Care Med. 2010;181:315-23.  Back to cited text no. 1
    
2.
Amelink M, de Groot JC, de Nijs SB, Lutter R, Zwinderman AH, Sterk PJ,et al. Severe adult-onset asthma: A distinct phenotype. J Allergy Clin Immunol 2013;132:336-41.  Back to cited text no. 2
    
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Black PN, Udy AA, Brodie SM. Sensitivity to fungal allergens is a risk factor for life-threatening asthma. Allergy 2000;55:501–4.  Back to cited text no. 3
    
4.
Fairs A, Agbetile J, Hargadon B, Bourne M, Monteiro WR, Brightling CE, et al. IgE sensitization to Aspergillus fumigatus is associated with reduced lung function in asthma. Am J Respir Crit Care Med 2010;182:1362-8.  Back to cited text no. 4
    
5.
O'Driscoll BR, Powell G, Chew F, et al. Comparison of skin prick tests with specific serum immunoglobulin e in the diagnosis of fungal sensitization in patients with severe asthma. Clin Exp Allergy. 2009;39:1677-83.  Back to cited text no. 5
    
6.
Agarwal R, Noel V, Aggarwal AN, Gupta D, Chakrabarti A. Clinical significance of Aspergillus sensitisation in bronchial asthma. Mycoses 2011;54:e531-8.  Back to cited text no. 6
    
7.
Woolnough KF, Richardson M, Newby C, et al. The relationship between biomarkers of fungal allergy and lung damage in asthma. Clin Exp Allergy. 2017;47:48–56.  Back to cited text no. 7
    
8.
Denning 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;179:11-8.  Back to cited text no. 8
    
9.
Goh JK, Yii ACA, Lapperre ST, Chan KW A, Chew, TF, Chotirmall, HS et al. Sensitization to Aspergillus species is associated with frequent exacerbations in severe asthma. J Asth Alller. 2017;10:131-140.  Back to cited text no. 9
    
10.
Agbetile J, Bourne M, Fairs A,et al. Effectiveness of voriconazole in the treatment of Aspergillus fumigatus-associated asthma (EVITA3 study) J Allergy Clin Immunol. 2014;134:33-9.  Back to cited text no. 10
    
11.
Global Initiative for Asthma (GINA); 2014. Available from: http://ginaasthma.org/archived-reports/. [Last accessed on 2016 Nov 16].  Back to cited text no. 11
    
12.
Shah A. Allergic bronchopulmonary aspergillosis. Indian J Chest Dis Allied Sci 1998;40:224-9.  Back to cited text no. 12
    
13.
Agarwal R. Controversies in allergic bronchopulmonary aspergillosis. Int J Respir Care 2010;5: 203-6.  Back to cited text no. 13
    
14.
Zureik M, Neukirch C, Leynaert B, Liard R, Bousquet J, Neukirch F. Sensitisation to airborne moulds and severity of asthma: cross sectional study from European Community respiratory health survey. BMJ 2002;325:411–4.  Back to cited text no. 14
    
15.
Targonski PV, Persky VW, Ramekrishnan V. Effect of environmental molds on risk of death from asthma during the pollen season. J Allergy Clin Immunol 1995;95:955-61.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
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