Prevalence of chronic pulmonary aspergillosis in fibrocavitary pulmonary tuberculosis patients

ABSTRACT

Background:

Tuberculosis (TB) is still a global health issue. While the lungs are the most commonly affected, infections can also affect other organs. Because of the rise in immunocompromised hosts, the number of opportunistic infections has skyrocketed. In instances of aspergilloma and chronic pulmonary aspergillosis (CPA), pulmonary tuberculosis (PTB) is the most usually linked condition.

Material and Methods:

The current cross-sectional study was conducted on 42 study participants from January 2018 to June 2019.

Results:

Aspergilloma was observed in two participants (4.8%) of the study population. Candida growth was observed in five participants (11.9%) of the study population on sputum fungal culture. Aspergillus growth and Candida growth was observed in three (7.1%) and two (4.8%) participants of the study population, respectively, on bronchoalveolar lavage (BAL) fungal culture. Aspergillus IgG antibody was positive in four particpants (9.5%) of study population. Out of the 42 participants, four were diagnosed with CPA.

Conclusion:

Since CPA and PTB patients present similar symptoms, it is virtually impossible to distinguish between the two unless serological test is performed. There has been a significant burden of patients with CPA, especially in post tuberculosis fibro-cavitation. CPA patients requires long-term anti-fungal therapy; hence an improved case detection should be undertaken.

Introduction

Tuberculosis (TB) has been the greatest destroyer of mankind since time immemorial. Pulmonary tuberculosis (PTB) and chronic pulmonary aspergillosis (CPA) present with similar symptoms. CPA is one of the important differential diagnosis of tuberculosis. CPA, unlike invasive aspergillosis, affects those who are immune to the infection. Morbidity is high, with both systemic and respiratory symptoms. Treated cases of pulmonary tuberculosis can lead to consequences, including decline in lung function, long standing pulmonary symptoms such as cough, haemoptysis, and chronic pulmonary aspergillosis (CPA).[1,2,3]

The fungus Aspergillus fumigatus is responsible for a number of lung illnesses, the clinical manifestations of which are dependent on the host’s immunological status.[4] Allergic bronchopulmonary aspergillosis (ABPA) can exacerbate asthma symptoms to variable degrees, whereas CPA is more commonly detected in PTB persistent cavities.[5] Aspergillus fumigatus is the most prevalent species responsible for CPA, which is a long-term Aspergillus colonisation of the lungs.

The majority of CPA patients have or have had a pulmonary ailment. Tuberculosis and atypical Mycobacterium infection are the most frequent illnesses. In comparison to colonisation, the existence of A. fumigates in a bronchoscopic sample is a significantly more prevalent infection.[4] CPA most typically develops in an existing bronchopulmonary or pleural cavity, although it can also induce the creation and enlargement of new cavities or nodules, as well as alveolar consolidation in rare cases. There might be a number of underlying issues.[6]

The purpose of this study was to determine the prevalence of CPA in patients with treated fibrocavitary PTB who were admitted to a tertiary care facility.

Materials and Methods

The current cross-sectional, observational study was carried out in Dr Panjabrao Deshmukh Memorial Medical College, a tertiary level healthcare hospital and medical college, over a period from January 2018 to June 2019 to assess the prevalence of CPA in treated fibrocavitary PTB cases attending the outpatient department (OPD) and inpatient department (IPD). Before the study began, clearance from the institutional ethics committee was obtained. Individuals who were more than 18 years of age, willing to participate in the study, and who had an X-ray suggestive of fibrocavitary pulmonary lesion and sputum for AFB negative were included in the study. Those patients who were hypotensive and had SpO₂ less than 90% on room air, and patients with bleeding diathesis were excluded from study. The sample size was calculated using OpenEpi software version 3 considering 95% confidence interval (CI) and 15% allowable error, the minimum sample size to achieve the desired objectives comes out to be 32. Thus, we studied a total of 42 study subjects who follow the inclusion and exclusion criteria.

The bronchial tree was examined using fiberoptic bronchoscopy, and bronchoalveolar lavage (BAL) fluid was obtained (BAL fluid fungal culture and BAL CB-NAAT). The bronchoscopy was conducted trans-nasally using a Fujinon bronchoscope by two bronchoscopists under local anaesthetic on all participants who had at least two sputum smear examinations that were negative for acid fast bacilli. The nasal and throat were sprayed with lignocaine 10% and the vocal cords, trachea, and bronchi were sprayed with lignocaine 2% solution. Premedication with midazolam 2–3 mg was used in few participants. Bronchial aspirate (BA) and BAL were obtained from the appropriate place after a comprehensive inspection of the bronchial tree. BAL samples were collected from all the patients with vital condition permitting bronchoscopy and following inclusion criteria and who consented to the procedure, under aseptic precaution and were sent to the microbiology department for KOH mount and fungal culture. Subsequently, the culture was examined. Pulmonary function testing (PFT) was done once the patient’s condition was stable before discharge. Chest X-ray with PA view was done for all the patients. Data was collected using a pre-designed questionnaire. The data was imported into Microsoft Excel and analysed with the Statistical Package for the Social Sciences (SPSS) software trial version 20.

Results

The present cross-sectional, observational study was conducted at Dr Panjabrao Deshmukh Memorial Medical College, a tertiary level healthcare hospital and medical college, over a period from January 2018 to June 2019 to assess prevalence of CPA in treated fibrocavitary PTB. Most of the study population belonged to the age group of more than 50 years (50%) followed by 31–40 years (21.4%), and 41–50 years (19%) with the mean age being 50 ± 13.88 years [Table 1]. There was slight male predominance (25, 59.5%) amongst the study population [Pie Diagram 1]. Cough (92.9%) was the most common clinical feature observed in the study population followed dyspnoea (85.7%), weight loss (35.7%), fever (28.6%), and haemoptysis (26.2%) [Table 2]. Most of the study population had productive cough (27, 64%) followed by dry cough (12, 29%) [Pie Diagram 2]. Dyspnoea was present in 36 study participants. Among that, most of the study population had modified Medical Research Council (mMRC) grade 1 dyspnoea (53%) followed by grade 2 (36%), and grade 3 (11%) [Table 3]. Out of all the participants, 15 had comorbidities. Diabetes was present in 19.05% of the participants followed by hypertension in 11.9%. Only 4.76% had chronic kidney disease [Table 4]. Obstructive (57.1%) was the most common PFT pattern followed by restrictive (38.1%) [Table 5]. On chest X-ray, only the fibrocavitary lesion was seen in 40 participants (95.2%) and fibrocavitary lesions with aspergilloma was observed in two particpants (4.8%) of the study population [Pie Diagram 3]. After conducting fungal culture of sputum, it was found that Candida growth was present in 11.9% of the study population [Table 6]. Aspergillus growth and Candida growth were observed in three (7.1%) and two (4.8%) participants of the study population, respectively, on BAL fungal culture. Aspergillus fumigatus species was detected in all positive cases [Table 7]. BAL sample was processed in Cartridge-Based Nuclear Acid Amplification Test (CB-NAAT) for detection of Mycobacterium tuberculosis (MTB) bacteria, and MTB was detected in two patients (4.8%). Aspergillus IgG antibody was positive for 9.5% of the study population [Table 8].

Table 1.

Distribution of patients according to age

Age Group (Years)	Frequency	Percentage
21-30	04	9.5
31-40	09	21.4
41-50	08	19.0
More than 50	21	50.0
Total	42	100.0

Pie Diagram 1.

Showing gender-wise distribution

Table 2.

Clinical features amongst study population

Clinical features	Frequency	Percentage
Cough	39	92.9
Dyspnoea	36	85.7
Haemoptysis	11	26.2
Weight loss	15	35.7
Fever	12	28.6

(*multiple choices)

Pie Diagram 2.

Distribution of study subjects according to type of cough

Table 3.

Grade of dyspnoea amongst the study population

mMRC grade	Frequency	Percentage
Grade 1	19	53
Grade 2	13	36
Grade 3	04	11
Grade 4	00	00
Total	36	100

Table 4.

Comorbidities amongst the study population

Comorbidities	Frequency	Percentage
Diabetes	8	19.05
Hypertension	5	11.90
Chronic kidney disease	2	4.76
Total	15	35.71

Table 5.

Pulmonary function test amongst the study population

Pulmonary Function Test	Frequency	Percentage
Not done	2	4.8
Obstructive	24	57.1
Restrictive	16	38.1
Total	42	100.0

Pie Diagram 3.

Distribution of study subjects according to X-ray findings

Table 6.

Sputum fungal culture amongst the study population

Sputum Fungal Culture	Frequency	Percentage
Candida growth	5	11.9
No growth	37	88.1
Total	42	100.0

Table 7.

BAL fungal cultures amongst the study population

BAL Fungal Culture	Frequency	Percentage
Aspergillus growth	3	7.1
Candida growth	2	4.8
No growth	37	88.1
Total	42	100.0

Table 8.

Aspergillus IgG antibodies amongst the study population

	Frequency	Percentage
Negative	38	90.5
Positive	4	9.5
Total	42	100.0

Discussion

The present cross-sectional, observational study was conducted at Dr Panjabrao Deshmukh Memorial Medical College, a tertiary level healthcare hospital and medical college, from January 2018 to June 2019 to assess the prevalence of CPA in treated fibrocavitary PTB. Most of the study population belonged to the age group more than 50 years (50%) followed by 31–40 years (21.4%), and 41–50 years (19%) with the mean age being 50 ± 13.88 years. This finding was similar to that of the study conducted by Shahid et al.,[7] in which the mean age was 49.94 ± 14.4 years, by Jain et al.,[8] in which the mean age was 42.8 ± 17.2 year, and by Iqbal et al.,[9] in which the mean age was 45 ± 15.7 years. There was slight male predominance (25, 59.5%) in the study population. Similarly, male predominance (60%) was reported in the study conducted by Jain et al.[8] This finding was similar to the study conducted by Iqbal et al.,[9] in which 69.6% were males.

In the present study, cough (92.9%) was the most common clinical feature observed in the study population followed dyspnoea (85.7%), weight loss (35.7%), fever (28.6%), and haemoptysis (26.2%). In the present study, most of the study participants had productive cough (64%) followed by dry cough (29%). This finding was similar to that of the study conducted by Iqbal et al.,[9] in which the most common symptoms were cough (63.76%), followed by fever (57.9%), haemoptysis (57.9%), and weight loss (28.9%).

In the present study, obstructive (24, 57.1%) was the most common PFT abnormality followed by restrictive (16, 38.1%). According to Dhooria et al.,[10] study presence of air flow obstruction on spirometry was significantly associated with Aspergillus sensitisation. There was a high prevalence of Aspergillus sensitisation in PTB-related fibrocavitary disease.

In the present study, only fibrocavitary lesion was seen in 40 participants (95.2%) and fibrocavitary lesion with aspergilloma was observed in two participants (4.8%) of the study population on chest X-rays. Similarly, in the study conducted by Jain et al.,[8] fibrocavitary lesion and aspergilloma were seen in 50% and 22.8% of patients on chest X-ray, respectively. Aspergilloma, if present on chest X-ray, can be of good diagnostic value.

In the present study, Candida growth was observed in 5 participants (11.9%) of the study population on sputum fungal culture. In the present study, Aspergillus growth and Candida growth were observed in three (7.1%) and two (4.8%) participants of study population, respectively, on BAL fungal culture. Aspergillus fumigatus was the species detected in all cultures. Similarly, in the study conducted by Iqbal et al.[9] BAL culture was positive for Aspergillus spp. in 46 participants (66.7%), and in the study by Shahid et al.[11] BAL culture was positive in 13 participants (14.7%) with Aspergillus fumigatus (9, 69.23%) being the most common species.

In the present study, MTB was detected in two patients on BAL CB-NAAT in order to exclude TB infection. In the present study, Aspergillus IgG antibody was positive in 4 participants (9.5%) of the study population. Similarly, it was reported that 13 participants (26%) were positive for Aspergillus antibody in the study conducted by Dhooria et al.[10] and 27 participants (30.6%) in the study conducted by Shahid et al.[7] Also, in a study conducted by Vijayachari et al.,[12] it was reported that Aspergillus culture and Aspergillus precipitin were positive in 25 (12.5%) and 27 (13.5%) cases, respectively. This further denotes the sensitivity of Aspergillus fumigatus IgG antibody test of about 90%. On correlating the culture with serological diagnosis in the present study, all patients with Aspergillus culture positivity had a serum IgG antibody test positive.

Serology has an extra edge over routine culture as the detection of antibody indicates that there is definite infection which induces antibody production, and this rules out the presence of fungus as mere contamination. Detection of Aspergillus in immunocompromised hosts with low immune response, combination of other serologic test like BAL Galactomannan, beta D glucan test and culture may help in diagnosis.

Conclusion

Since CPA and PTB patients present with similar symptoms, it is virtually impossible to distinguish between them unless a serological test is performed. There has been a significant burden of patients with CPA especially in post tuberculosis fibro-cavitation. CPA patients require long-term anti-fungal therapy; hence an improved case detection should be undertaken.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.