Inhalant allergens especially spore forming fungi like Aspergillus, play a key role in bringing upon inflammation in the airways.[1] The fungi derive its name from its resemblance to the brush aspergillum, used for sprinkling holy water. The ubiquitous spores inhaled by everyone though seldom have any effect in healthy individuals, are trapped in thick and viscid secretions in asthmatic subjects which on continuous inhalation triggers asthma. The clinical spectrum of Aspergillus associated hypersensitivity respiratory disorders include Aspergillus induced asthma, allergic bronchopulmonary aspergillosis, allergic aspergillus sinusitis.[2] Hypersensitivity pneumonitis may also be caused by Aspergillus, but is generally seen in non atopic individuals.
Aspergillus induced asthma is yet to receive the recognition that it deserves. Aspergillus sensitization in patients with asthma not only increases the severity of the disease but also is responsible for clinical entities like allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis. It is thus crucial to screen all asthmatic subjects for sensitization to Aspergillus antigens so as to identify those at risk. Here in this study it was attempted to find out the prevalence of Aspergillus hypersensitivity in bronchial asthma patients presenting to a tertiary medical college in Kerala. No study on the topic has been conducted in this part of the state even though prevalence of bronchial asthma is on the rise. By early identification of Aspergillus hypersensitivity, necessary precautions and close follow up may be planned to prevent serious complications that they are prone to later. This study benefited those asthmatic patients with undetected Aspergillus hypersensitivity by an early diagnosis.
Materials and Methods
Objectives of study: The objectives of this study were to study the clinical profile of patients with bronchial asthma presenting to our hospital, know the most prevalent subspecies of Aspergillus causing sensitisation in bronchial asthma in our locality and to know the association between Aspergillus antigen hypersensitivity and severity of bronchial asthma.
Study area: The study was a hospital based non-interventional observational cross sectional study conducted in MES Medical College Hospital, Perinthalmanna, Malappuram, Kerala.
Study period: Study period was taken as one year
Study Population
Inclusion criteria: All the people more than fifteen years of age presented to MES Medical College during the period of study with at least one of the three below mentioned conditions were included in the study irrespective of sex and locality. The conditions were 1) patients diagnosed to have bronchial asthma, 2) patients with history of recurrent or episodic attacks of chest tightness, breathlessness and cough (especially nocturnal), 3) patients who had wheeze on auscultation of chest.
Exclusion criteria: The people excluded from study were 1) those aged less than 15 years and more than 70 years, 2) those with diagnosis of allergic bronchopulmonary aspergillosis or chronic obstructive pulmonary disease, 3) pregnant women, 4) those with immunosuppressive conditions such as chronic liver disease, renal failure, uncontrolled diabetes mellitus, chronic heart failure, immunosuppressive drugs other than glucocorticoids for controlling asthma and 5) those not willing to give informed consent.
Sample size: After applying the above inclusion and exclusion criteria 100 patients were included in the study.
Data collection technique and tools: After getting informed consent meticulous clinical history of all patients were taken. It included present symptoms, allergy to dust, smoke or smell, history of atopy, eczema or food allergy and number of hospitalization in a year. Co-morbidities were enquired of along with relevant personal history. Thorough general and respiratory system examination were done and positive findings were noted. Assessment of severity of asthma was carried according to the 2002 Global Initiative for Asthma (GINA) recommendations (given below in table 1), which include the effect of treatment on disease severity.
Mean age group of the study population was found out as 41.7 ± 13.4 years. Most of the studies showed a male predominance pattern. The difference here may be due to exposure to dust and smoke from traditional type of kitchens as most of the female population in my study were housewives and a significant number are allergic to dust and smoke. In a multicentre study conducted in India by Dr. S.K.Jindal et al sponsored by Indian Council of Medical Research, it had been found out that females outnumbered males with a male female ratio of 0.63 in South India and almost 70% women of study population were housewives.[4] This finding was also brought out by a study in Spain in 2013 by Martínez-Moragón E et al where mean age of study population was 50 years, 64.6% were women and majority were house wives and unemployed.[5] Cough was the predominant symptom in all the above studies. Past history of atopy was noted in 31%. 20% of study population had atopy in a similar study in Vishakapattanam.[6] Allergy to dust, smoke or both were noticed in 97% of my study population which is the highest in any study to date. The pulmonary function tests were done before and after bronchodilation in all the hundred patients. The mean values were furnished above in results. There was significant reversibility noticed among the pre and post bronchodilation spirometries. Most significant reduction in mean was noted in Forced Expiratory Volume for 1st second, followed by peak expiratory flow rate. Pulmonary function tests worsened over increasing age as well. The values were very much identical to the one found out by Madan et al in Punjab.[7] Pascual et al reported that clinically, airflow obstruction in asthma often is not fully reversible, and many asthmatic subjects experience an accelerated and progressive loss of lung function over time.[8] Lange et al proved that adults with asthma have substantially greater declines in forced expiratory volume in 1s (FEV1) over time in comparison with healthy subjects.[9]
Prevalence of Aspergillus antigen hypersensitivity in this study population was noted as 34%. Aspergillus fumigates hypersensitivity was seen among 27 out of 34 hypersensitive patients (79.4%) closely followed by A.niger (61.8%), A.flavus (55.9%) and A.terreus (41.2%). Many were hypersensitive to multiple aspergillus antigen and a few were hypersensitive to all four tested. The reported frequency of aspergillus sensitivity in patients with asthma had varied from 16-38% in different parts of world and in a study from Delhi 30 out of 105 patients with asthma revealed to have hypersensitivity to aspergillus antigen.[10] The investigators also recorded that a positive Aspergillus skin test was related to severity of airway obstruction such that asthma was more severe in patients hypersensitive to Aspergillus than to other allergens. A European committee respiratory health survey in 30 centres demonstrated that the frequency of sensitization to Alternaria alternata and Cladosporium herbarum increased significantly with increasing asthma severity.[11] Previous studies have shown that sensitization or exposure to fungi increases the risk of death from asthma and also acute attacks of asthma requiring intensive care unit admissions.[12,13]
In this study day time symptoms, nocturnal symptoms, loss of activities and need for rescuer medications were significantly higher in patients with Aspergillus antigen hypersensitivity. Generally severity of asthma was more among patients with Aspergillus antigen hypersensitivity. 76.5% of hypersensitive group had experienced day time symptoms more than twice/week. 76.5% had nocturnal symptoms and 73.5% needed rescuer medications for more than twice a week. There are no much Indian studies and none from this area of country to compare these findings. Seasonal variation was also found significantly higher among my study population with Aspergillus antigen hypersensitivity which was again, a unique finding. Respiratory signs were significantly more among the group who were hypersensitive to Aspergillus antigen. Polyphonic wheeze was heard in 91.2% of the patients who were hypersensitive to aspergillus where as majority of patients (57.6%) who were not hypersensitive had normal breath sounds with no added sounds. Worsening of asthma clinically with Aspergillus antigen hypersensitivity had been brought to notice prior by Ownby DR et al.[14] Pulmonary function test was also done in all patients. Mean forced expiratory volume in 1st second before bronchodilator administration was 54% in hypersensitive group compared to 74% in non hypersensitive group. After administration of bronchodilator, means improved to 69% in hypersensitive group and 82.8% in non hypersensitive groups. The differences in means were statistically significant and there was a significant reduction in forced expiratory volume in 1st second among those patients hypersensitive to Aspergillus antigen. Similarly mean forced vital capacity was 56.1% before bronchodilator administration and 71.4% after bronchodilator administration among hypersensitive group compared to 74.7% and 83.1% among non hypersensitive group respectively. Again mean forced vital capacities before and after bronchodilator administration were significantly low among those hypersensitive to Aspergillus antigen. The same applied to mean FEV1/FVC. It was significantly low among those hypersensitive to Aspergillus antigen (82.9) compared to those not hypersensitive (90.8). Mean Peak Expiratory Flow Rates before and after bronchodilator administration among those not hypersensitive to Aspergillus antigen were 74.2 and 84.7 respectively. That was also significantly low in those hypersensitive to Aspergillus antigen, the values being 56 and 69.1 respectively. So pulmonary function test showed more detrimental pattern in those hypersensitive to Aspergillus antigen than the rest who were not. Similar patterns were obtained in studies conducted by Nichols et al.[15]
