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ORIGINAL ARTICLE
Year : 2023  |  Volume : 22  |  Issue : 1  |  Page : 77-81  

Nontubercular bacterial and fungal infections in patients of chronic obstructive pulmonary disease


1 Department of Medicine, K.G.M.U., Lucknow, Uttar Pradesh, India
2 Department of Respiratory Medicine, K.G.M.U., Lucknow, Uttar Pradesh, India

Date of Submission07-Sep-2021
Date of Acceptance01-Jun-2022
Date of Web Publication24-Jan-2023

Correspondence Address:
Shyam Chand Chaudhary
Department of Medicine, K.G.M.U., Lucknow - 226 016, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aam.aam_186_21

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   Abstract 


Introduction: Acute exacerbation of chronic obstructive pulmonary disease (COPD), frequently due to respiratory tract infection is the major cause of morbidity and mortality, and estimate suggests that it is currently the third leading cause of death worldwide. Aims and Objectives: This study aims to study the prevalence of nontubercular bacterial and fungal infections in patients of COPD. Materials and Methods: It is an observational study done for 1-year period from August 2017 to July 2018. A total of 100 COPD patients who fulfilled the inclusion and exclusion criteria were analyzed in the present study. These cases were classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) combined assessment criteria and subjected to sputum or in some cases Bronchoalveolar lavage (BAL) fluid examination for nontubercular bacterial and fungal pathogens. Serum galactomannan assay, bronchoscopy, and computed tomography chest were done in selected cases. Results: The age of the study population ranged from 40 to 85 years and the mean age was 60.01 ± 9.85 years. Majority of the patients were male (81.0%) and most (78.0%) of them were smokers. Most of the patients belonged to GOLD Grades 2 and 3. Forty-six percent of the patients did show pathogenic organisms in sputum examination. Out of these, 80.4% were bacterial, mainly Gram-negative organisms (Acinetobacter, Pseudomonas, Escherichia coli, Enterobacter, Proteus, and Citrobacter) and 19.6% of cases were having fungal infections (Candida and Aspergillus). Conclusions: Increasing patient age, smoking habit, and severity of COPD were related to an increasing frequency of bacterial and fungal infections. Early detection and proper treatment could help in preventing the morbidity and mortality related to COPD.

   Abstract in French 

Résumé
Introduction: L'exacerbation aiguë de la maladie pulmonaire obstructive chronique (MPOC), souvent en raison de l'infection des voies respiratoires, est la principale cause de morbidité et de mortalité, et l'estimation suggère qu'il s'agit actuellement de la troisième cause de décès dans le monde. Objectifs et objectifs: Cette étude vise à étudier la prévalence des infections bactériennes et fongiques non tubulaires chez les patients de la MPOC. Matériaux et méthodes: Il s'agit d'une étude d'observation réalisée pour une période de 1 an d'août 2017 à juillet 2018. Un total de 100 patients atteints de MPOC qui remplissaient les critères d'inclusion et d'exclusion ont été analysés dans la présente étude. Ces cas ont été classés selon l'initiative globale des critères d'évaluation combinés chroniques obstructifs (OR) et soumis à des expectorations ou dans certains cas examen des liquides de lavage bronchoalvéolaire (BAL) pour les agents pathogènes bactéries et fongiques non tubulaires. Le test de galactomannane sérique, la bronchoscopie et le poitrine de tomodensitométrie ont été effectués dans certains cas. Résultats: L'âge de la population d'étude variait de 40 à 85 ans et l'âge moyen était de 60,01 ± 9,85 ans. La majorité des patients étaient des hommes (81,0%) et la plupart (78,0%) d'entre eux étaient des fumeurs. La plupart des patients appartenaient à GOLD GRADES 2 et 3. Quarante-six pour cent des patients ont montré des organismes pathogènes à l'examen des expectorations. Parmi ceux-ci, 80,4% étaient des organismes bactériens, principalement à Gram - négatifs (Acinetobacter, Pseudomonas, Escherichia coli, Enterobacter, Proteus et Citrobacter) et 19,6% des cas avaient des infections fongiques (Candida et 23 aspergillus). Conclusions: L'âge croissant du patient, l'habitude du tabagisme et la gravité de la MPOC étaient liés à une fréquence croissante des infections bactériennes et fongiques. La détection précoce et le traitement approprié pourraient aider à prévenir la morbidité et la mortalité liées à la MPOC.
Mots-clés: Maladie pulmonaire obstructive chronique, infection fongique, initiative mondiale pour la maladie pulmonaire obstructive chronique, infection bactérienne non tuberculeuse

Keywords: Chronic obstructive pulmonary disease, fungal infection, Global Initiative for Chronic Obstructive Lung Disease, nontubercular bacterial infection


How to cite this article:
Khandelwal A, Chaudhary SC, Verma AK, Sawlani KK, Gupta KK, Himanshu D, Sonkar SK, Verma SK. Nontubercular bacterial and fungal infections in patients of chronic obstructive pulmonary disease. Ann Afr Med 2023;22:77-81

How to cite this URL:
Khandelwal A, Chaudhary SC, Verma AK, Sawlani KK, Gupta KK, Himanshu D, Sonkar SK, Verma SK. Nontubercular bacterial and fungal infections in patients of chronic obstructive pulmonary disease. Ann Afr Med [serial online] 2023 [cited 2023 Feb 1];22:77-81. Available from: https://www.annalsafrmed.org/text.asp?2023/22/1/77/368400




   Introduction Top


According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), chronic obstructive pulmonary disease (COPD) is defined as a preventable and treatable disease with significant extrapulmonary effects that may contribute to its severity in individual patients. COPD is a major cause of chronic morbidity and mortality worldwide. It has an extensive, adverse effect on both patients and the health-care system with high resource utilization, which includes frequent clinician office visits, frequent hospitalizations due to acute exacerbations, and chronic therapy. Hence, it has become a disease of increasing public health importance throughout the world.[1]

In COPD, the innate lung defense appears to be disrupted as a result of exposure to smoke and other environmental irritants. This impairment in lung defense mechanism results in increased probability of infection that could contribute to progressive loss of lung function. Historically, bacteria were considered the main infective cause of exacerbations but with the development of new diagnostic techniques, respiratory viruses are also frequently detected in COPD exacerbations.

The British hypothesis proposed that recurrent bronchial infections were the reason that some smokers developed airflow obstruction while others did not.[2],[3],[4] Bacterial and viral coinfection present in 25% of exacerbations and is associated with worse clinical outcomes and more severe disease.[5],[6],[7] Previous studies had focused on bacterial diversity, but very few have reported on fungal diversity.


   Materials and Methods Top


This cross-sectional study was conducted in the department of medicine and department of respiratory medicine at a tertiary care hospital for 1 year from August 2017 to July 2018 in Northern India. A total of 116 cases of COPD, age >40 years who gave written consent were included in the study. Out of 116 patients, 12 patients were detected sputum positive for tuberculosis and four patients expired during hospitalization. Therefore, only the findings of 100 patients were analyzed. Exclusion criteria include sputum positivity for tuberculosis, patients on antituberculous treatment, cases of empyema thoraces, patients with a well-documented chronic history of heart failure, liver cirrhosis, and those who denied for consent.

Methodology

A detailed clinical history and physical examination were carried out for every subject. In the clinical history symptoms (dyspnea, sputum production, wheeze, and cough) using Modified Medical Research Council (mMRC) grading and COPD Assessment Test (CAT) score, duration of COPD, and history of exacerbation including prior hospitalization and treatment history were elicited. History of the presence of risk factors such as smoking (number of pack-years smoked and current smoking status), cooking habit, occupational and environmental exposure, hypertension, and presence of any other chronic disease was inquired. Thereafter, detailed general and systemic physical examinations were carried out. After clinical details, patients fulfilling the inclusion criteria were then subjected to sputum examination and other baseline investigations necessary to rule out other comorbid conditions such as chest X-ray P/A view, electrocardiogram, complete blood count, liver and kidney function test, random blood sugar, Arterial Blood Gas (ABG), and spirometry. Sputum, and in some patients bronchoalveolar lavage sample was examined for Gram stain, Acid Fast Bacilli stain, fungal elements and cultures. During the hospital stay, the patients were treated by the consultant doctor as per the requirement of the cases. Data were entered in structured tables for comparison where the population in the study was divided into groups according to the GOLD criteria and sputum growth. Serum galactomannan, contrast-enhanced computed tomography (CECT), and high-resolution CT chest and bronchoscopy were also done in selected patients who did not respond to appropriate antibacterial treatment. Spirometry and determination of COPD severity ‒ spirometry was done during the hospital stay or during discharge from the hospital, some patients who were not able to do spirometry test were tested postdischarge, as per the ATS guidelines. On the basis of spirometry, the severity of dyspnea using mMRC scale or symptoms using CAT score, and history of moderate & severe exacerbation (including prior hospitalization), patients were classified into GOLD COPD class.

Statistical analysis

The statistical analysis was done using the SPSS (Statistical Package for the Social Sciences) version 21.0 (International Business Machines Corporation, Armonk, State-New York, Country-United State) statistical analysis software. The values were represented in number (%) and mean ± standard deviation. The level of significance “P” mentioned in the results was considered significant if P < 0.05. Ethical clearance and funding: This study was approved by the Institutional Ethical Committee and was not supported by any funding agency.


   Results Top


A total of 100 COPD patients fulfilling the inclusion and exclusion criteria were analyzed. The age of patients enrolled in the study ranged from 40 to 85 years, the median age is 60 years, whereas the mean age of patients was 60.01 ± 9.85 years. Majority of the patients enrolled in the study were aged 51–70 years (68.0%). Only 10.0% of patients were aged >70 years. Majority of the COPD patients enrolled in the study were male (81.0%) and the male/female ratio was 4.26:1. Most (78.0%) of the patients enrolled in the study were smokers. The distribution of the study population based on spirometry findings is shown in [Table 1].
Table 1: Distribution of study population according to spirometric severity grade (n=100)

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COPD cases were also classified according to the GOLD grade as shown in [Table 2]. Grade 1 (1A + 1B) was the least common grade (4.0%), and none of the patients enrolled had Grade 4. The most common grade was Grade 2 and Grade 3. Of which, the most common were Grade 2B (23.0%) and Grade 3B (17.0%).
Table 2: Distribution of study population according to the Global Initiative for Chronic Obstructive Lung Disease grading (n=100)

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Pathogenic growth in sputum specimens observed in our COPD patients is tabulated in [Table 3]. Out of 37 patients which showed bacterial infections, there was a predominance of Gram-negative bacteria with Acinetobacter (21.6%), Pseudomonas (16.2%), Escherichia coli (16.2%), Enterobacter (8%), Proteus (5%), and Citrobacter (3%) as a predominant organism, whereas Gram-positive bacteria seen were Staphylococcus aureus and Enterococci, 10.8% each. Nine patients also showed fungal infection candida spp. (55.5%) and Aspergillus infection (44.5%). Patients who were positive for Aspergillus, three out of four patients also had serum galactomannan positive and two underwent bronchoscopy which was also positive for Aspergillus. CECT of the thorax was done in two patients who only showed findings of COPD without any evidence of cavity or fungal ball.
Table 3: Sputum culture findings in study population (n=100)

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The number of patients with sputum culture positive was predominantly seen in older age groups, i.e., 61–70 years (47.8% vs. 24.1%) and >70 years (17.4% vs. 3.7%). This difference was found to be statistically significant (P = 0.003). Most of the patients having bacterial growth in sputum (83.8%) were smokers, whereas patients having fungal growth (55.6%) were nonsmokers. The association between the type of pathogenic growth and smoking status among COPD patients was found to be statistically significant (P = 0.013).

No pathogenic growth was found in GOLD Grade 1, whereas pathogenic growth was found to be higher among GOLD Grade 3 (3B, 3C, and 3D). This association was found to be statistically significant (P = 0.014). Although proportional differences in GOLD grade of COPD patients with the presence of bacterial and fungal growth were observed, these differences were not found to be statistically significant [Table 4].
Table 4: Association of the Global Initiative for Chronic Obstructive Lung Disease grading of bacterial and fungal growth

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CT of the thorax was done in 19 cases and its findings were suggestive of COPD and consolidation which was of confirmatory value only without any fungal ball or cavity.


   Discussion Top


Studies conducted by Bhattacharyya et al. and Chaudhary et al. observed that the mean age of COPD patients was 65.32 ± 9.58 and 57.75 ± 9.81 years, respectively, which are comparable to our study (60.01 ± 9.85).[8],[9] Out of 100 patients, 81% were male, and male: female ratio was 4.26:1. The reason for this difference is that in India, COPD is more prevalent among males due to the higher prevalence of smoking habits as compared to females. Gupta et al. also found 88% of males in their study population, which is similar to our finding.[10] A study conducted on the Indian population by Jindal et al. observed the overall higher prevalence of COPD in men (5%) as compared to women (3.2%).[11]

In a study done by Gupta et al. in 83 COPD patients, out of which 82% (28 current smokers and 40 former smokers) were smokers and their finding was similar to our observation. Majority of males (98%) were smokers and females were nonsmokers but most of the female patients had a history of exposure to cooking fuels in their past.[10] The difference in smoking status of males and females enrolled in the study was found to be statistically significant (P < 0.001). In the study of Devi P et al., out of 100 COPD patients, 85 were males and the majority of them (83) were smokers.[12] Hogg et al. have described the presence of lymphoid follicles in the airway walls of ex-smokers that have a key role in driving inflammation and airflow obstruction in COPD.[13] This inflammation persists after smoking. Neutrophils, macrophages, and T-cells produce mediators such as cytokines, reactive oxygen species, and proteases to drive this process.[14],[15],[16]

Most of our COPD patients were in Grade 2 and Grade 3. Of which, the most common were Grade 2B (23.0%) and Grade 3B (17.0%). Out of 100 patients, 46 patients did show sputum growth. Thirty-seven patients (80%) showed bacterial growth, whereas 9 (20%) patients showed fungal growth. Miravitlles et al. studied that in patients of COPD, both stable and acute exacerbation prevalence of bacterial infection was around 50% which is very similar to our results.[17],[18]

The colonization of the upper respiratory tract microbiome is a dynamic process with frequent turnover of different strains. A number of these bacteria are potentially pathogenic microorganisms if they move into the lower respiratory tract.[19] These potential pathogens may colonize the upper airway for long periods such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae, or transient periods of Mycoplasma pneumonia.[20],[21] Sethi et al. have described that the acquisition of a new strain of bacteria is associated with COPD exacerbations.[22] There are challenges in obtaining a representative sample, but studies of sputum and bronchoscopy samples using standard culture and molecular techniques have clearly demonstrated that COPD exacerbations are associated with a markedly increased prevalence of bacteria.

Out of 37 patients who showed bacterial infections, there was a predominance of Gram-negative bacteria with Acinetobacter, Pseudomonas, E. coli, Enterobacter, Proteus, and Citrobacter as predominant, whereas Gram-positive bacteria seen were S. aureus and Enterococci. The diversity of bacteria isolated was different from the study conducted previously by Sethi et al. but a possible explanation is a predominance of severe COPD patients in our study shifting diversity of bacteria which is comparable with the study of Monsó et al.'s study in patients of severe and very severe COPD, which showed increasing prevalence of bacteria such as Pseudomonas and E. coli.[23] Other reasons for contrasting results could be increased usage of antibiotics in primary and secondary care that has led to either increased prevalence of drug-resistant species (which are different from the normal spectrum of COPD patients) or detection of nonpathogenic growth since most of them are treated outside before coming to tertiary care.

Although initially fungus was initially considered normal saprophytes present in the oral cavity including candida and Aspergillus species. However, Aspergillus species may be responsible for important clinical events and can lead to rapidly invasive and life-threatening disseminated diseases, depending on the host immune status and the presence of underlying lung disease.[24],[25] Patients with severe COPD who often receive broad-spectrum antibiotics and corticosteroids are now acknowledged to be one of the main risk groups for pulmonary aspergillosis.[26],[27],[28] In the article by Chen et al. in which pulmonary fungal infections were compiled, Candida glabrata was reported in 4 out of 140 patients.[29] Candida pneumonia is caused either by candidemia through the hematogeneous route or by aspiration from the oropharynx, and there are increasing case reports showing candida spp. infections in patients of COPD.[30]

In our study, nine patients also showed fungal infection candida spp. (55.5%) and Aspergillus infection (44.5%). Previously only individual studies have been done in fungal infections and COPD. Bitar et al. and Neofytos et al. both have independently shown the prevalence of candidemia and Aspergillus as the most common fungal lung infection.[31],[32] Su J et al used molecular microbiological technique to provide insight into both fungal and bacterial diversities in acute exacerbation of COPD patiens during hospitalization. In respect to fungal infection their observation was similar to our study.[33]


   Conclusions Top


COPD has always been associated with a bacterial infection. Its presence can lead to exacerbation and worsening of disease-causing increase in the hospital stay. Previous studies have shown that bacteria such as H. influenza and Moraxella as predominant infection in COPD patients. However, in our study, predominant bacteria seen were Acinetobacter, Pseudomonas, Enterobacter, E. coli, and S. aureus. This could be due to the fact that in our study, predominant patients were indoor patients which were mostly referred and had Forced Expiratory volume in the first second (FEV1) <50%.

The prevalence of fungal infection in COPD patients is not known, however, prime fungal infections seen were Aspergillus and candida. One should always suspect fungal infection in copd patients who are not improving after appropriate bacterial treatment.

Thus, we want to conclude by stating that COPD is a treatable disease; early detection intervention and proper treatment (depending on the pathogen) could help in preventing mortality and morbidity associated with the disease.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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