Respiratory morbidities and lung function abnormalities in survivors of Bhopal Gas Disaster: A cross-sectional study.

BACKGROUND: Respiratory morbidities remained significant for the last four decades among the survivors of the Bhopal gas disaster. We hypothesized that lung function abnormalities, especially small airway dysfunctions, were responsible for the ongoing respiratory morbidities. METHODS: We conducted a cross-sectional study between 2018 and 2020 in the severely exposed cohort of the Bhopal gas disaster. A standardized questionnaire was used to record their respiratory symptoms. The forced oscillometry (FOT) and spirometry were utilized for assessing lung functions. Univariate and multivariate logistic regression analyses were used to examine the association. RESULTS: Of 916 enrolled individuals (men: 442, mean age: 55.2 ± 12.3 years), 558 participated in lung function assessments. Breathlessness was the most common complaint (71.7%), followed by cough (15.1%). The R5 > upper limit of normal (ULN), R5-19 > ULN, and X5 < lower limit of normal (LLN) were observed in 29.3%, 23.3%, and 21.2% participants, respectively. Normal, obstructive, and restrictive spirometry was observed in 46.2%, 26.1%, and 27.7%, participants, respectively. FOT parameters were abnormal in 25.3% individuals with normal spirometry. Individuals with obstructive spirometry had the highest risk of having abnormal FOT parameters (adjusted odds ratio [adj OR]:3.93, 95% confidence interval [CI]: 2.24-6.89). Breathlessness showed a significant association with abnormal R5 (adj OR: 1.81; 95% CI: 1.13-2.91) and obstructive spirometry (adj OR: 2.26; 95% CI: 1.29-3.95). CONCLUSIONS: Assessment of small airway functions along with spirometry are useful to identify complex lung function abnormalities in cases of toxic inhalation.

Oxidative biomarkers of exhaled breath condensate in adults exposed to traffic-related air pollution: a case-control study.

Traffic-related air pollution exposure (TRAP) is a major public health problem. The effects of TRAP exposure on the oxidative biomarkers of exhaled breath condensate (EBC) of adults are seldom studied. We compared the oxidative EBC biomarkers in a group of individuals exposed to TRAP with those of individuals unexposed to TRAP. We conducted a case-control study in Bhopal City (Madhya Pradesh, India). Adults with a history of exposure to TRAP were enrolled as cases and adults with less exposure to TRAP were used as a control. Based on respiratory symptoms and smoking habits, study subjects were stratified into six subgroups. EBC was collected by TURBO14 (Medivac SRL, Italy) at -5 °C. The EBC pH was measured after gas standardization with argon. EBC hydrogen peroxide (H2O2), cystenine leukotrienes (Cys-LTs), 8-isoprostane were measured by commercial ELISA kit. A total of 250 consecutive adult (male: 194) subjects were recruited. Among them, 133 were TRAP-exposed (male: 128) and 117 were non-TRAP-exposed (male: 66). The respiratory symptoms between TRAP-exposed and non-TRAP-exposed subjects were not different. The post-gas standardized EBC pH (median: 7.72; interquartile range (IQR): 7.15-7.94 vs. median: 7.60, IQR: 6.72-7.87;p= 0.09) and EBC H2O2(median: 2.20µmol l-1; IQR: 1.46-3.51 vs. median: 1.99, IQR: 1.41-3.10;p= 0.29) in TRAP-exposed subjects were statistically not different from the non-TRAP-exposed subjects. The EBC Cys-LTs (median: 69.81; IQR: 57.0-83.38 vs. median: 47.21 pg ml-1; IQR: 39.90-54.87,p< 0.001) and EBC 8-isoprostane (median: 12.55 pg ml-1; IQR: 5.51-18.09 vs. median: 7.12; IQR: 4.60-16.04,p= 0.026) in TRAP-exposed subjects were higher compared to those in non-TRAP-exposed subjects. The subgroup analysis showed that TRAP-exposed subjects, irrespective of their smoking habits and respiratory symptoms, had higher EBC Cys-LTs compared to the non-TRAP-exposed subjects. TRAP exposure increases oxidative biomarkers of the EBC in adults.

Elevated serum matrix metalloprotease (MMP-2) as a candidate biomarker for stable COPD.

BACKGROUND: The increasing trend of Chronic Obstructive Pulmonary Disease (COPD) in becoming the third leading cause of deaths by 2020 is of great concern, globally as well as in India. Dysregulation of protease/anti-protease balance in COPD has been reported to cause tissue destruction, inflammation and airway remodelling; which are peculiar characteristics of COPD. Therefore, it is imperative to explore various serum proteases involved in COPD pathogenesis, as candidate biomarkers. COPD and Asthma often have overlapping symptoms and therefore involvement of certain proteases in their pathogenesis would render accurate diagnosis of COPD to be difficult. METHODS: Serum samples from controls, COPD and Asthma patients were collected after requisite institutional ethics committee approvals. The preliminary analysis qualitatively and quantitatively analyzed various serum proteases by ELISA and mass spectrometry techniques. In order to identify a distinct biomarker of COPD, serum neutrophil elastase (NE) and matrix metalloprotease-2 (MMP-2) from COPD and Asthma patients were compared; as these proteases tend to have overlapping activities in both the diseases. A quantitative analysis of the reactive oxygen species (ROS) in the serum of controls and COPD patients was also performed. Statistical analysis for estimation of p-values was performed using unpaired t-test with 95% confidence interval. RESULTS: Amongst the significantly elevated proteases in COPD patients vs the controls- neutrophil elastase (NE) [P < 0.0241], caspase-7 [P < 0.0001] and matrix metalloprotease-2 (MMP-2) [P < 0.0001] were observed, along with increased levels of reactive oxygen species (ROS) [P < 0.0001]. The serum dipeptidyl peptidase-IV (DPP-IV) [P < 0.0010) concentration was found to be decreased in COPD patients as compared to controls. Interestingly, a distinct elevation of MMP-2 was observed only in COPD patients, but not in Asthma, as compared to controls. Mass spectrometry analysis further identified significant alterations (fold-change) in various proteases (carboxy peptidase, MMP-2 and human leukocyte elastase), anti-proteases (Preg. zone protein, α-2 macroglobulin, peptidase inhibitor) and signalling mediators (cytokine suppressor- SOCS-3). CONCLUSION: The preliminary study of various serum proteases in stable COPD patients distinctly identified elevated MMP-2 as a candidate biomarker for COPD, subject to its validation in large cohort studies.

Regression equations of respiratory impedance of Indian adults measured by forced oscillation technique.

BACKGROUND: Forced oscillation technique (FOT) is a technique to measure the mechanical properties of the lung. The present study was aimed to develop regression equations of within- and whole-breath respiratory impedance (Zrs) of healthy Indian adults. METHODS: Total 323 adults were sequentially screened. Smokers, individuals with respiratory symptoms or diseases, and unable to perform acceptable FOT were excluded. Within- and whole-breath resistance (Rrs) and reactance (Xrs) were measured at 5, 11, and 19 Hz by Resmon Pro® Full device. The regression equations of within- and whole-breath Rrs and Xrs were generated separately for men and women by multiple linear regression models. RESULTS: The FOT data of 253 individuals (122 men) aged 18-81 years were included in the analysis. The magnitudes of whole-breath Rrs at 5 Hz (4.53 ± 1.05 cmH2O/L/s in women vs. 3.26 ± 1.05 cmH2O/L/s in men; P = 0.000) and whole-breath Xrs at 5 Hz (-1.23 ± 0.66 cmH2O/L/s in women vs. -1.00 ± 0.54 cmH2O/L/s in men; P = 0.003) of women were significantly of higher magnitude as compared to men. The standing height was the best determinant of Zrs, followed by body weight; the effect of age was negligible and was observed in men only. The magnitudes of both Rrs and Xrs decrease with an increase in standing height of both men and women. CONCLUSIONS: The present study provides regression equations of within- and whole-breath respiratory impedance of Indian adults.

Regression Equations of Respiratory Impedance Measured by Forced Oscillation Technique for Indian Children.

OBJECTIVE: To develop regression equations of within and whole-breath respiratory impedance for Indian children aged 5 to 17 y. METHODS: A prospective cross-sectional study was carried out in 5 to 17 y old school children of Bhopal, India. Healthy children were identified by physical examination and by administering questionnaire. The respiratory system resistance (Rrs) and reactance (Xrs) were measured at frequency of 5, 11, and 19 Hz by forced oscillation technique (FOT). The regression equations of within and whole-breath Rrs and Xrs were developed separately for boys and girls by multiple linear regression models. RESULTS: Total 336 children were recruited and data of 320 healthy children (boys - 159), standing height of 146.1 ± 16.6 cm and body mass index of 17.2 ± 2.9 kg/m2 were included in the analysis. The mean respiratory system resistance at 5 Hz (R5) and respiratory system reactance at 5 Hz (X5) of the children, irrespective of gender were 5.46 ± 2.10 cmH2O/L/s and - 1.43 ± 0.85 cmH2O/L/s respectively. Boys of age 16 y and older had significantly smaller Rrs as compared to girls of corresponding age (p < 0.05). The standing height of children had the highest predictive power, followed by age in the regression model. With an increase in standing height, the magnitude of both Rrs and Xrs values of children decrease. The bodyweight of children had a negligible contribution to the regression models. CONCLUSIONS: The regression equations of within- and whole-breath Rrs and Xrs of Indian children aged 5 to 17 y are presented for the first time. The R5 values of Indian children were comparable to children of other ethnicities.

Effect of age at exposure on chromosome abnormalities in MIC-exposed Bhopal population detected 30 years post-disaster.

Follow-up cytogenetic study was carried out on 145 individuals from areas stratified by Indian Council of Medical Research, for evaluation of the effect of age-at-exposure and its interaction with exposure status on chromosomal aberrations (CA) in blood-lymphocytes. CA was presented as abnormal cell (Abc), aberrations (Abn) and number of aberration/abnormal cell (Abn/Abc), and correlated with age-at-exposure (childhood: <1-10 years; young: 11-26 years; adult: >27 years). Age related increase in abnormalities (Abc, Abn, Abn/Abc) was observed in all exposure strata, except moderately exposed adult-group, which has exhibited lower Abn/Abc than similarly exposed childhood and young age-groups. Elevation of CA was also related to exposure status. Abn/Abc frequency was significantly higher in the severely exposed young and adult groups compared to the controls of the same age. Two-way ANOVA revealed significant abnormalities between the exposed groups; however, interaction of age and exposure was not statistically significant. Significant difference in group-means of Abc and Abn was also observed between adult and childhood in Tukey HSD test. Altogether, a significant interaction of age and MIC-exposure on CA could not be established due to inter-individual variation and lack of baseline information on CA. Significantly higher Abn was observed in people consuming tobacco; however, interaction of lifestyle with additional environmental/occupational exposures during last 30 years against a background exposure to MIC remained un-elucidated. Nevertheless, the study was important for demonstration of the correlation of the current status of CA in circulating lymphocytes with age and exposure status of the MIC-exposed survivors.