Association of the C allele of rs479200 in the EGLN1 gene with COVID-19 severity in Indian population: a novel finding.

The present study investigated two single nucleotide polymorphisms (SNPs)-rs479200 and rs516651 in the host EGLN1/PHD2 gene for their association with COVID-19 severity. A retrospective cohort of 158 COVID-19 patients from the Indian population (March 2020 to June 2021) was enrolled. Notably, the frequency of C allele (0.664) was twofold higher than T allele (0.336) in severe COVID-19 patients. Here, we report a novel finding that the C allele of rs479200 in the EGLN1 gene imparts a high risk of severe COVID-19 (odds ratio-6.214 (1.84-20.99) p = 0.003; 9.421 (2.019-43.957) p = 0.004), in additive inheritance model (adjusted and unadjusted, respectively).

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.

Oscillometry-Defined Small Airway Dysfunction in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: The prevalence of small airway dysfunction (SAD) in patients with chronic obstructive pulmonary disease (COPD) across different ethnicities is poorly understood. This study aimed to estimate the prevalence of SAD in stable COPD patients. METHODS: We conducted a cross-sectional study of 196 consecutive stable COPD patients. We measured pre- and post-bronchodilator (BD) lung function and respiratory impedance. The severity of COPD and lung function abnormalities was graded in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. SAD was defined as either difference in whole-breath resistance at 5 and 19 Hz > upper limit of normal or respiratory system reactance at 5 Hz < lower limit of normal. RESULTS: The cohort consisted of 95.9% men, with an average age of 66.3 years. The mean forced expiratory volume 1 second (FEV1) % predicted was 56.4%. The median COPD assessment test (CAT) scores were 14. The prevalence of post-BD SAD across the GOLD grades 1 to 4 was 14.3%, 51.1%, 91%, and 100%, respectively. The post-BD SAD and expiratory flow limitation at tidal breath (EFLT) were present in 62.8% (95% confidence interval [CI], 56.1 to 69.9) and 28.1% (95% CI, 21.9 to 34.2), respectively. COPD patients with SAD had higher CAT scores (15.5 vs. 12.8, p<0.01); poor lung function (FEV1% predicted 46.6% vs. 72.8%, p<0.01); lower diffusion capacity for CO (4.8 mmol/min/kPa vs. 5.6 mmol/min/kPa, p<0.01); hyperinflation (ratio of residual volume to total lung capacity % predicted: 159.7% vs. 129%, p<0.01), and shorter 6-minute walk distance (367.5 m vs. 390 m, p=0.02). CONCLUSION: SAD is present across all severities of COPD. The prevalence of SAD increases with disease severity. SAD is associated with poor lung function and higher symptom burden. Severe SAD is indicated by the presence of EFLT.

CD14 C-159T polymorphism and its association with chronic lung diseases: A pilot study on isocyanate exposed population of Central India.

CONTEXT: CD14 functions as a multifunctional receptor for bacterial cell wall components including endotoxin and lipopolysaccharide and is likely to influence the cytokine profile and subsequent immunoglobulin E production in response to antigen/allergen contact in allergic phenotypes. AIMS: The present study was to investigate genetic polymorphism in CD14 gene - 159C/T, which may be one of the risk factor for increased prevalence of Chronic Lung Diseases in the Central India. SETTINGS AND DESIGN: Survivors of Methyl isocyanates toxicity in Bhopal still suffering from various respiratory ailments were examined. MATERIALS AND METHODS: Polymerase chain reaction-restriction fragment length polymorphism was performed to determine the polymorphism of C-159T. RESULTS: The genotype and allelic frequencies were in Hardy-Weinberg's equilibrium. Prevalence of CC, CT, and TT were 5.5%, 22.2% and 9.25% respectively in asthmatics; 16.6%, 20.3% and 5.5% respectively in chronic obstructive pulmonary disease (COPD) patients and 5.5%, 14.8% and 1.85 respectively among interstitial lung disorder (ILD) patients; whereas the control cohort with no methyl isocyanate exposure displayed (CC, CT, and TT) cytosine, thymine as 2%, 1.6% and 2% respectively. Increased risk of Asthma among those carrying TT genotype and T allele (odds ratio [OR] =2.61 and 2.02 respectively). CONCLUSION: COPD risk significantly found among those with CC genotype and C allele (OR = 2.81 and 1.50 respectively), whereas ILD risk found significantly among CT genotype and C allele (OR = 1.75 and 1.40 respectively). Therefore, single nucleotide polymorphism (SNP) C-159T polymorphism in CD14 gene might be a risk factor for development of CLD in this population.

Exploring the Immunodominant Epitopes of SARS-CoV-2 Nucleocapsid Protein as Exposure Biomarker.

Background The nucleocapsid protein (N protein) of SARS-CoV-2 is undeniably a potent target for the development of diagnostic tools due to its abundant expression and lower immune evasion pressure compared to spike (S) protein. Methods Blood samples of active COVID-19 infections (n=71) and post-COVID-19 (n=11) were collected from a tertiary care hospital in India; pre-COVID-19 (n=12) sera samples served as controls. Real-time reverse transcriptase-PCR (rRT-PCR) confirmed pooled sera samples (n=5) were used with PEPperCHIP® SARS-CoV-2 Proteome Microarray (PEPperPRINT GmbH, Germany) to screen immunodominant epitopes of SARS-CoV-2. Highly immunodominant epitopes were then commercially synthesized and further validated for their immunoreactivity by dot-blot and ELISA. Results The lowest detectable concentration (LDC) of the N1 peptide in the dot-blot assay was 12.5 µg demonstrating it to be fairly immunoreactive compared to control sera. IgG titers against the contiguous peptide (N2: 156AIVLQLPQGTTLPKGFYAEGS176) was found to be significantly higher (p=0.018) in post-COVID-19 compared to pre-COVID-19 control sera. These results suggested that N2-specific IgG titers buildup over time as expected in post-COVID-19 sera samples, while a non-significant immunoreactivity of the N2 peptide was also observed in active-COVID-19 sera samples. However, there were no significant differences in the total IgG titers between active COVID-19 infections, post-COVID-19 and pre-COVID-19 controls. Conclusion The N2-specific IgG titers in post-COVID-19 samples demonstrated the potential of N protein as an exposure biomarker, particularly in sero-surveillance studies.

Retrospective analysis of lung function abnormalities of Bhopal gas tragedy affected population.

BACKGROUND & OBJECTIVES: A large numbers of subjects were exposed to the aerosol of methyl isocyanate (MIC) during Bhopal gas disaster and lung was one of the most commonly affected organs. The aim of the present study was to analyze retrospectively the lung function abnormalities among the surviving MIC exposed population (gas victims) and to compare it with the non-MIC exposed (non gas exposed) population. METHODS: The spirometry data of both gas victims and non gas exposed population who attended the Bhopal Memorial Hospital & Research Centre for evaluation of their respiratory complaints from August 2001 to December 2009, were retrospectively evaluated and compared. RESULTS: A total 4782 gas victims and 1190 non gas exposed individuals performed spirometry during the study period. Among the gas victims, obstructive pattern was the commonest (50.8%) spirometric abnormality followed by restrictive pattern (13.3%). The increased relative risk of developing restrictive abnormality among gas victims was observed in 20-29 yr age group only (adjusted relative risk: 2.94, P<0.001). Male gas victims were more affected by severe airflow obstruction than females and the overall increased relative risk (1.33 to 1.45, P<0.001) of developing obstructive pattern among gas victims was observed. INTERPRETATION & CONCLUSIONS: The present study showed that the relative risk for pulmonary function abnormalities in gas victims was significantly more among those who were young at the time of disaster. Increased smoking habit among gas victims might have played an additive effect on predominance of obstructive pattern in spirometry.

Body mass index among patient with chronic obstructive pulmonary diseases.

Body mass index (BMI) is one of the important parameter to assess functional status of patients with Chronic Obstructive Pulmonary Disease (COPD). The aim of present study was to assess the prevalence of underweight among clinically stable COPD patients and relationship of BMI with increasing severity of COPD. COPD was defined as a subject who had post-bronchodilator FEV1/FVC < lower limit of normal, age more than 40 years and either current or ex smoker. Spirometry data of 7412 subjects were retrospectively analyzed and 1269 COPD patients and 1202 bronchial asthma patients were identified. The severity of airflow obstruction was classified as per GOLD guideline. The BMI of each patient was calculated from weight and height. The BMI of COPD patients were compared with bronchial asthma. The average BMI of COPD patients and bronchial asthma patients were 20.2 +/- 4.3 kg/m2 and 23.2 +/- 5.4 kg/m2 respectively. Overall, 38% COPD patients were underweight (BMI < 18.5 kg/m2) and irrespective of severity of the disease, proportion of underweight COPD patient was significantly more as compared to bronchial asthma patients (P < 0.001). The mean BMI also reduces significantly with progression of COPD severity.

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.

Assessment of severity of methaemoglobinemia following fibreoptic bronchoscopy with lidocaine.

BACKGROUND: Lidocaine is commonly used for topical anaesthesia during fibreoptic bronchoscopy (FOB) and it can cause methaemoglobinemia. The present study was undertaken to evaluate the severity of post-bronchoscopy methaemoglobinemia while using lidocaine as a topical anaesthetic agent. METHODS: We prospectively studied consecutive adult patients who underwent diagnostic FOB in our institution. Blood methaemoglobin levels were estimated by co-oximetry before bronchoscopy and one hour after first instillation of lidocaine. Occurrence of symptoms suggestive of mild methaemoglobinemia (i.e., fatigue, palpitation, dizziness, nausea and headache) were recorded in a severity scale before collection of post-bronchoscopy blood samples. RESULTS: A total of 48 adult patients were enrolled in this study. The mean amount of lidocaine used for bronchoscopy during this study was 7.4 +/- 1.4 mg/kg body weight. The mean pre- and post-bronchoscopy methaemoglobin levels were 0.44 mg/mL and 0.80 mg/mL, respectively. After bronchoscopy, severe and very severe symptoms were reported by 2.1% to 10.4% patients. However, severities of the symptoms were unrelated to post-bronchoscopy methaemoglobin level or the amount of lidocaine used during the FOB. CONCLUSIONS: Blood methaemoglobin levels following FOB remained within the physiological limits when British Thoracic Society recommended dose of lidocaine was used. However, few patients had symptoms similar to mild methaemoglobinemia after FOB.

Prevalence of depression in stable chronic obstructive pulmonary disease.

BACKGROUND: Psychological impairment is a significant co-morbid condition of chronic obstructive pulmonary disease (COPD). No studies from India have been conducted to assess the prevalence of depression in COPD. METHODS: We investigated the prevalence of depression in 100 consecutive stable COPD patients during their routine outpatient department visits. Patients diagnosed to have depression or chronic systemic diseases were excluded. Severity of the COPD was classified according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. Hindi translations of patient health questionnaire-9 (PHQ-9) were administered and severity of depression was assessed at each stage of the COPD. RESULTS: All subjects were males with a mean age of 61.7 +/- 9.6 years. Six patients in stage I, 32 patients in stage II, 40 patients in stage III and 22 patients in stage IV of the COPD were enrolled. The cumulative prevalence of depression in the study population was 72 percent. CONCLUSIONS: Symptoms of depression were observed at all stages of COPD and its severity increased with an increase in severity of the COPD. High prevalence of depressive symptoms in Indian patients with COPD may be due to various confounding factors. Screening for symptoms of depression in patients with COPD by simple and quick validated questionnaires during their out-patient visits will be helpful in early diagnosis and appropriate treatment or referral.

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.

Long-term ambient air pollution exposure and respiratory impedance in children: A cross-sectional study.

OBJECTIVES: The present study was aimed to compare the respiratory impedance of children residing in areas with different ambient air pollution (AAP). METHODS: A comparative cross-sectional pilot study was carried out in healthy school children of two cities in India i.e. Agra and Bhopal. Agra is one of the most polluted cities of India and AAP of Agra is much higher as compared to Bhopal, the reference city in the present study. The respiratory impedance was measured at 5, 11, and 19 Hz by forced oscillation technique (FOT). The anthropometric parameters, respiratory resistance at 5 Hz (R5), small airway resistance (R5-19), and reparatory reactance at 5 Hz (X5) of children from above two cities were compared by Student's t-test. RESULTS: A total 114 children (57 boys) from Agra and 151 children (76 boys) from Bhopal aged 9-16 years were recruited. The children from Agra were younger (11.9 ±â€¯1.9 yr vs. 13.1 ±â€¯2.2 yr, p < 0.001) as compared to Bhopal, though their anthropometric parameters were comparable. The magnitude of R5 (5.53 ±â€¯1.81 cmH20/L/s vs. 5.10 ±â€¯1.77 cmH20/L/s, p = 0.05), X5 (-1.46 ±â€¯0.65 cmH20/L/s vs. -1.17 ±â€¯0.63 cmH20/L/s, p < 0.001), and R5-19 (0.79 ±â€¯0.79 cmH20/L/s vs. 0.56 ±â€¯0.78 cmH20/L/s, p = 0.023) in children of Agra were higher as compared to children of Bhopal. The differences in impedance were significantly higher between boys, but not between girls. CONCLUSIONS: The present study demonstrates a higher magnitude of small airway dysfunction in children exposed to high AAP. A future study involving larger samples and longitudinal measurements of respiratory impedance will provide better insights.

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.

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.

Respiratory Morbidity of Roadside Shopkeepers Exposed to Traffic-related Air Pollution in Bhopal, India.

BACKGROUND: Traffic-related air pollution (TRAP) is a major source of ambient air pollution in urban areas. Shopkeepers of heavily trafficked roadside shops are persistently exposed to high levels of TRAP. OBJECTIVES: To estimate the prevalence of respiratory morbidity in shopkeepers of shops in heavily trafficked roadside areas in Bhopal city (India) and to determine any association with long term exposure to TRAP. METHODS: This cross-sectional study was conducted among 251 shopkeepers working in roadside shops of three major traffic corridors in Bhopal city. The demographic profile and prevalence of respiratory morbidity were collected by administering a validated questionnaire. The total exposure period (TEP) to TRAP was calculated for each individual by multiplying their work duration (in years) and average working hours per day. Odds ratios were calculated to estimate the association of TEP with respiratory morbidity. RESULTS: The age of the study population was 44.8±13.5 years old and 95% were male. Nearly 55% of the shopkeepers reported at least one respiratory symptom. The prevalence of bronchial asthma, chronic bronchitis, breathlessness, and cough was 3.6% (95% confidence interval (CI): 1.9-6.7), 13.9% (95% CI: 10.2-18.8), 41.8% (95% CI: 35.9-48.0), and 18.3% (95% CI: 14.0-23.6), respectively. The adjusted risk ratios of bronchial asthma 2.17 (95% CI: 0.35-13.41), chronic bronchitis 1.42 (95% CI: 0.58-3.48), breathlessness 1.71 (95% CI: 0.94-3.11), and cough 0.97 (95% CI: 0.47-2.03) for those with a TEP over 100. CONCLUSIONS: Shopkeepers working in heavily trafficked roadside shops suffer from respiratory morbidity and the risk increases with higher TEP. Total exposure period is a valuable indicator to estimate the effects of long-term TRAP exposure. INFORMED CONSENT: Obtained. ETHICS APPROVAL: The study was approved by the Institutional Ethics Committee of the National Institute for Research in Environmental Health (Bhopal, India). COMPETING INTERESTS: The authors declare no competing financial interests.

Post intubation tracheal stenosis.

Tracheal stenosis following prolonged intubation is a relatively rare but a serious problem. However, some degree of airway injury is common following intubation, no matter whether it is prolonged or of short duration. Here, we are reporting a fifty six year old male patient who developed multiple web like tracheal stenosis following intubation with high volume low pressure cuff endotracheal tube. Subsequently, the stenosis was successfully dilated by balloon bronchoplasty.

Role of Proteases in Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is generally associated with progressive destruction of airways and lung parenchyma. Various factors play an important role in the development and progression of COPD, like imbalance of proteases, environmental and genetic factors and oxidative stress. This review is specifically focused on the role of proteases and their imbalance in COPD. There are three classes (serine, mettalo, and cysteine) of proteases involved in COPD. In serine proteases, neutrophil elastase, cathepsin G, and proteinase-3 are involved in destruction of alveolar tissue. Matrix-mettaloproteinase-9, 12, 13, plays an influential role in severity of COPD. Among cysteine proteases, caspase-3, caspases-8 and caspase-9 play an important role in controlling apoptosis. These proteases activities can be regulated by inhibitors like α-1-antitrypsin, neutrophil elastase inhibitor, and leukocyte protease inhibitor. Studies suggest that neutrophil elastase may be a therapeutic target for COPD, and specific inhibitor against this enzyme has potential role to control the disease. Current study suggests that Dipeptidyl Peptidase IV is a potential marker for COPD. Since the expression of proteases and its inhibitors play an important role in COPD pathogenesis, therefore, it is worth investigating the role of proteases and their regulation. Understanding the biochemical basis of COPD pathogenesis using advanced tools in protease biochemistry and aiming toward translational research from bench-to-bedside will have great impact to deal with this health problem.