Factors influencing COPD long term doxycyclne responsiveness: An appraisal
Debkanya Dey1, Sudipto Saha2, Rajat Banerjee3, Parthasarathi Bhattacharyya4
1Department of Biotechnology and Dr. B. C Guha Centre for Genetic Engineering and Biotechnology, University of Calcutta, Kolkata, West Bengal, India, 2Bioinformatics Centre, Bose Institute, Kolkata, West Bengal, India, 3Biotechnology and Dr. B. C Guha Centre for Genetic Engineering and Biotechnology, Ballygunge Science College, University of Calcutta, Kolkata West Bengal, India, 4Pulmonology Institute of Pulmocare and Research, Kolkata, West Bengal, India. E-mail: titirdey1@gmail.com
Background: Doxycycline, a tetracycline possessing anti-MMP property has shown improvement in lung function on long term use in COPD patients as an add-on to standard therapy. The response, however, is not uniform in all patents.
Objective: The aim of the study is to investigate the differences between the responsive and unresponsive group.
Methods: Subjects from institutional, prospective, randomized, ethically approved long term doxycycline clinical trial were selected on the basis of their lung function changes at 6 months of the add-on therapy with doxycycline. The patients were divided into responsive and unresponsive groups and their clinical parameters and spirometric variables were evaluated statistically.
Results: Out of 52 COPD patients on add-on therapy 33 (63.46%) were responsive and 19 (36.53%) were unresponsive at 6 months to doxycycline therapy. The responsive subjects had shown improvement in predicted percentage of FEV1 and FEV1 absolute (ml) significantly (p<0.001) while those unresponsive has significant worsening of the same parameters along with FEF25-75 and FEV1/FVC (p<0.01). The unresponsive group had a significantly lower BMI (p value <0.5) and a trend of higher frequency of exacerbation (47.37% vs 30.30%) and shortness of breath (89.47% vs 72.73%). Partial least square discriminant analysis revealed that the discriminating factors between the two groups are lung function, amount of usage of biomass fuel, age, and BMI.
Conclusion: Doxycycline responsive and unresponsive COPD patients could be distinct phenotypes with certain discriminating factors. Higher recruitment and further evaluation are essential to elaborate on this area.
Comparision of lung functions and functional capacity in patients of COPD through pulmonary function test and incremental shuttle walk test
Komal Bhavik Shah
Department of Pulmonology, Jaslok Hospital and Research Center, Mumbai, Maharashtra, India. E-mail: komaljasani@yahoo.com
Background: COPD patients often exhibit reduced functional capacity in addition to impaired lung functions. However, how these 2 components relate to each other still remains to be established. Objective of this study was to examine relationship between lung functions (FEV1 and MVV - determined by PFT) and functional capacity (distance walked - determined by incremental shuttle walk test) in COPD patients. Pulmonary function test is an established tool to measure lung functions. ISWT is less popular but standardized, incremental, externally paced test which requires minimum instruments or infrastructure. It provokes a symptom limited maximal performance and provides objective measurement of disability.
Methods: Study was performed in 45 COPD patients in OPD. First PFT was performed followed by ISWT more than 30 minutes apart, on the same day, as per standard protocols. FEV1, MVV, and total distance walked was calculated and compared with statistical analysis.
Results: Study performed on 45 COPD patients (34 Males, 11 Females), including 48.90 % (22 patients) moderate COPD and 33.3% (15 patients) severe COPD. It showed statistically significant correlation between FEV1, MVV and total distance walked in ISWT in linear regression (p-0.002).
Conclusion: Our study shows that ISWT results strongly correlate with the PFT value. Hence, in addition to PFT, ISWT can be used as a supportive tool for an overall structural and functional diagnostic and prognostic assessment of COPD patients.
Cricoid cartilage augmentation using costal cartilage graft in the treatment of complex crico-tracheal stenosis in adults – An effective solution for a critical disease – A single centre experience
Vivek Vishwas Mundale, Mohan Venkatesh Pulle, Harsh Vardhan Puri, Belal Bin Asaf, Arvind Kumar
Institute of Chest Surgery, Medanta – The Medicity, Gurguram, Haryana, India. E-mail: mailvvm@gmail.com
Background and Objective: Crico-tracheal stenosis is a special entity, where stenosis involves trachea as well as cricoid cartilage. Costal cartilage augmentation of Cricoid is used commonly in paediatric age group. However, similar studies in adult population are lacking. Our objective is to study the outcomes of cricoid augmentation in treatment of complex crico-tracheal stenosis in adults.
Methods: A total of 8 patients, operated in a thoracic surgery unit at a tertiary care hospital were included. CT neck + thorax with 3D reconstruction and bronchoscopy were done before planning surgery. Decision to perform cricoid augmentation was taken intra-operatively. When indicated - Anterior cricoid split was done first followed by posterior cricoid split, only if required. The costal cartilage was harvested, reshaped, inserted as a wedge between the cut ends of cricoid and then fixed followed by crico-tracheal anastomosis. Injury to vocal cords and recurrent laryngeal nerve was avoided carefully. The result were considered “excellent” if voice, respiration and bronchoscopic examination are completely normal, “satisfactory” in case of mild hoarseness or shortness of breath on exercise above normal activity, and “poor” if patient developed anastomotic dehiscence, restenosis or vocal cord paralysis.
Results: All the 8 patients were extubated on table. One patient (stenosis post tracheo-bronchial tuberculosis) developed minimal dehiscence followed by recurrent stenosis which was successfully treated with dilatations. Rest all the patients had excellent outcome.
| Case number | Age | Sex | Cause of stenosis | Cotton-Myer grading of stenosis | Cricoid augmentation | Length of trachea resected (cm) | Postoperative outcome |
|---|---|---|---|---|---|---|---|
| 1 | 48 | Male | Intubation | III | Anterior | 2 | Excellent |
| 2 | 26 | Female | Intubation | III | Anterior | 4 | Excellent |
| 3 | 32 | Female | Tuberculosis | III | Anterior | 3.5 | Poor - Dehiscence and restenosis |
| 4 | 58 | Male | Intubation | IV | Anterior | 3.5 | Excellent |
| 5 | 33 | Female | Trauma | III | Anterior + posterior | 3 | Excellent |
| 6 | 26 | Male | Tracheostomy | IV | Anterior | 4.5 | Excellent |
| 7 | 42 | Female | Rheumatoid arthritis | III | Anterior + posterior | 3 | Excellent |
| 8 | 22 | Female | Intubation | III | Anterior | 3.5 | Excellent |
Conclusion: Cricoid augmentation using costal cartilage graft is safe, feasible and can be considered as a viable option in surgical treatment of crico-tracheal stenosis in adults.
Estimation of Blood eosinophil counts in smoker, nonsmoker COPD patients and healthy controls in an Indian cohort -A case control study
Nandini Dikshit, Surya Kant, Jyoti Bajpai, Anmary Royson, Ankita Mandal
Department of Respiratory Medicine, KGMU, UP, Lucknow. Email: dikshitnandini@gmail.com
Background: Eosinophilic inflammation is thought to be a characteristic feature of asthma rather than COPD. However, studies have shown that a subset of COPD patients with eosinophilic airway inflammation exists and are at an increased risk of exacerbation .It is a matter of further research that whether smoking is responsible for this eosinophilic inflammation or not .Our study is just a ripple in the vast ocean of Medical science to establish this relation.
Methods: 100 patients of age group 18-65 years having documented COPD diagnosed by the diagnostic criteria defined in GOLD 2021 were enrolled and levels of absolute eosinophil counts were estimated and compared .80 healthy non-smoker controls belonging to the same socio demographic profile were also enrolled for comparison.
Observations and Results: 100 COPD patients enrolled in the study and were divided into two groups according to their smoking status and 70 % were active or former smokers. Majority of patients were between the age group of 45-60 years .However, there was significant difference in age distribution of smokers and non-smokers. The mean age of smokers was significantly higher than non-smokers .Overall in our study males were predominant and absolute eosinophil counts was higher in COPD patients who were non-smokers versus those who were smokers .On the other hand total leucocyte counts were significantly higher in smokers as compared to non-smokers.
Conclusion: Pathways behind airway inflammation in COPD are complex and in our study eosinophilic inflammation has shown to be an emerging marker for defining phenotypes of COPD.
Evaluation of serum uric acid levels in patients of chronic obstructive pulmonary disease during acute exacerbation
Athira Parameswaran1, K. B. Gupta1, Ashuma Sachdeva2, Vipul Kumar1
1Department of Respiratory Medicine, PGIMS, Rohtak, Haryana, India, 2Department of Biochemistry, PGIMS, Rohtak, Haryana, India. E-mail: athiraparamu@gmail.com
Background: Serum uric acid is a simple, inexpensive and cheaply available test for assessing severity, risk stratification and avert premature death in COPD as compared to other biomarkers.
Objectives: To evaluate the relation between serum uric acid levels with selected demographic and clinical parameters during acute exacerbation, discharge and follow-up of patients with COPD.
Methodology: 110 patients admitted with acute exacerbation of COPD were selected and grouped as per GOLD staging and serum uric acid level was evaluated by enzymatic method. Serum uric acid level >6mg/dl for male and >7 mg/dl for female were considered as high.
Results: Mean serum uric acid level at the time of admission - 7.04, Discharge – 6.04, after 1 month – 5.581. 38.2% patient had - uric acid level 6-7 mg/dl, 34.5% patients had - 8-9 mg/dl. patients who were in GOLD stage 2-4 had uric acid 6-7 mg/dl. 58% of patients were lying in GOLD Stage 3-4. Irrespective of gender COPD patients with uric acid 6-9mg/dl had ≥1 acute exacerbations in last one year and patients with uric acid 8-11 mg/dl had ≥1 ICU admissions in last one year.66% of patients with uric acid level showed 6-9 mg/dl – moderate to severe pulmonary hypertension.
Conclusion: Serum uric acid is extensively and easily available, easy to interpret, low-cost biomarker which might have a role in identifying COPD patients who are at an increased risk of bad outcomes and require early care.
Development of a clinical score for the use of nebulizers in primary care through consensus by an expert working group
Sundeep Salvi1, Shrikant Pawar2, Ashfaq Hasan3, Aloke Ghosal4, Raja Dhar5, Subodh K. Katiyar6, K. S. Satish7, Deepak Talwar8, Surinder K. Jindal1
1Chest Research and Training (CREST), Pune, Maharashtra, India, 2Department of Pulmonary Medicine, Jindal Clinics, Chandigarh, India, 3Department of Pulmonary Medicine, Deccan College of Medical Sciences, Hyderabad, Telangana, India, 4National Allergy Asthma Bronchitis Institute, Kolkata, West Bengal, India, 5Department of Pulmonary Medicine, CK Birla Hospitals, Kolkata, West Bengal, India, 6Chest Care Centre, Kanpur, Uttar Pradesh, India, 7Department of Pulmonary Medicine, Fortis Hospital, Bengaluru, Karnataka, India, 8Metro Centre for Respiratory Diseases, Noida, Uttar Pradesh, India. E-mail: sundeepsalvi@gmail.com
Background: The use of nebulizers is an important and useful method for delivering drugs to the lungs in patients with various airway and lung parenchymal disorders. Use of nebulization had markedly increased during the COVID-19 pandemic. This had raised concerns about the potential spread of infection to others in the surroundings exposed to the virus dissemination through aerosolized particles. We considered it necessary to ensure appropriate use of nebulizers by primary care physicians and therefore developed a simple nebulization score to decide when to use nebulizers.
Methods: An expert working group (EWG) of pulmonologists was formed who using a semi-Delphi method developed a list of variables and a cut-off score. The EWG started with 55 variables developed through an exhaustive review of literature. These were further reduced to smaller number that had the maximum score as well as concordance with the EWG. The scores ranged from 1-10 (completely disagree to completely agree) and only those above 7.5 were selected.
Results: A total of 8 variables with the highest scores were selected [Table 1] which had a total maximum score of 40. A score of <15 was suggested to indicate “not-to use” and >20 to suggest a “definite-use” of nebulizer. A score between 15–20 was suggested “to use as per physician judgement”. A separate table of 12 conditions was made where use of nebulizers was mandatory.
Table 1.
List of variables selected for nebulizer scoring
| Number | Criteria | Score |
|---|---|---|
| 1 | Disease specific | |
| Asthma | 1 | |
| COPD | 2 | |
| 2 | Disease severity (asthma or COPD) | |
| Mild-to-moderate | 1 | |
| Severe | 6 | |
| 3 | Patient previously using inhalers with benefit | |
| pMDI, pMDI + spacer, DPI | 0 | |
| Nebulizer | 4 | |
| 4 | Noncompliance with the use of use of pMDIs with spacer and DPIs or persistent use of nebulizers, despite best efforts to encourage use of pMDIs or DPIs in patients | 6 |
| 5 | Distressing or disabling breathlessness despite maximal therapy with inhalers and feels better with nebulizer | 7 |
| 6 | Severe co-existing COPD in patients with lung cancer | 5 |
| 7 | Inability to inhale quickly and deeply using a DPI despite best efforts to train patients at DPI usage | 5 |
| Only for patients with COVID-19/other viral infections | ||
| 8 | COVID-19 positive/patients with other contagious viral infections | 3* |
| Total maximum score | 40 |
*If the patient is already on a pMDI or DPI and uses it correctly and is happy to continue with that, we should encourage them to use that. COPD: Chronic obstructive pulmonary disease, pMDI: Pressurised metered dose inhalers, DPI: Dry powder inhalers
Conclusion: This first of its kind nebulizer score should be used by primary care physicians to decide which patients should be put on nebulization treatment.
Blood eosinophil count levels among 1700 healthy, asthmatic and COPD subjects across India: Results from the nationwide respiratory research network study
Raja Dhar1, Malay Sarkar2, Arjun Padmanabhan3, Mohan Kumar Thekkinkattil4, Virendra Singh5, Nagesh Dhadge6, Gayathri Devi H. Jayadevappa7, Arpan Shah8, Sonali Trivedi9, Sameer Arbat10, Saibal Moitra11, Vijay Tyagi12, Rajesh Swarnakar13, Sahebrao Toke14, Suresh Anantraj15, Zuber Ahmed16, Sanjay Kochar17, Shrikant Krishnmurthy18, D. J. Christopher19, Priyanka Dhumal20, Swapnil Gadhave20, Sundeep Salvi20
1Asthma and Bronchitis Institute, Kolkata, West Bengal, India, 2IGMC, Shimla, Himachal Pradesh, India, 3Kerala Institute of Medical Sciences, Thiruvananthapuram, Kerala, India, 4One Care Medical Center, Coimbatore, Tamil Nadu, India, 5Asthma Bhawan, Jaipur, Rajasthan, India, 6Central Health Services, Pune, Maharashtra, India, 7MS Ramaiah Medical College, Bengaluru, Karnataka, India, 8Pranayam Lung and Heart Institute and Research Centre, Vadodara, Gujarat, India, 9 JLN Hospital and RC, Bhilai, Chattisgarh, India, 10KRIMS Hospitals, Nagpur, Maharashtra, India, 11Hindustan Park Apollo Gleneagles Hospital, Kolkata, West Bengal, India, 12Chest Centre/Metro Hospital and Heart Institute, Meerut and Yash Chest, Allergy and Rehabilitation Centre, Meerut, Uttar Pradesh, India, 13Department of Pulmonology, Getwell Hospital and Research Institute, Nagpur, Maharashtra, India, 14Pawana Hospital, Pune, Maharashtra, India, 15Sundaram Medical Foundation and SRM Institute for Medical Sciences, Chennai, Tamil Nadu, India, 16J. N. Medical College, AMU, Aligarh, Uttar Pradesh, India, 17S.P. Medical College, Bikaner, Rajasthan, India, 18Sri Bala Medical Centre and Hospital, Coimbatore, Tamil Nadu, India, 19Christian Medical College, Vellore, Tamil Nadu, India, 20Pulmocare Research and Education Foundation, Pune, Maharashtra, India. E-mail: docaardee@yahoo.com
Background: Blood eosinophil counts are important determinants of pharmacotherapy in patients with COPD. We aimed to study the absolute eosinophil count levels in healthy Indian subjects and compare them with patients with asthma and COPD across multiple centres in India.
Methods: The longitudinal, prospective study was conducted across 20 sites in India. Healthy subjects who came for routine health check-up, doctor diagnosed asthma and COPD subjects were recruited into the study. After obtaining informed consent, a structured questionnaire was administered to subjects to capture their demographic and health-related information and blood was collected for routine hemogram and sent to standard labs.
Results: We report the interim results of 1700 subjects an ongoing study in India. We enrolled 574 Asthmatic, 303 COPD, and 823 healthy participants. The median (IQR) absolute eosinophil counts (cells/µL) among healthy, asthmatic and COPD subjects were 185 (101-300), 310 (170-255), 204 (130-320). Asthmatics had significantly higher eosinophil counts than healthy and COPD subjects (p<0.05). Among asthmatics and COPD patients the absolute eosinophil counts were significantly higher in nonsmokers (both p values<0.05) than smokers, there is no such relationship was found in healthy participants.
Conclusion: To the best of our knowledge, this is the first nationwide study that has compared blood eosinophil levels between healthy, asthmatic and COPD subjects. Asthmatics as a group had the highest blood eosinophil levels. Although all groups had normal absolute eosinophil counts when measured as a median, there was a wide heterogeneity in eosinophil levels across all groups.
Global asthma network study: Adequacy of diagnosis and treatment in patients with symptoms of asthma
Sheetu Singh, Sundeep Salvi, Daya Krishan Mangal, Meenu Singh, Shally Awasthi, Padukuduru Anand Mahesh, Sushil K. Kabra, Sabir Mohammed, Thevaruparambil U. Sukumaran, Aloke G. Ghoshal, Monica Barne, Sanjeev Sinha, Sanjay K. Kochar, Nishtha Singh, Udaiveer Singh, Kamalesh Kumar Patel, Arvind Kumar Sharma, Bhushan Girase, Anil Chauhan, Niranjan Sit, Jayaraj B. Siddaiah, Virendra Singh
Department of Pulmonary Medicine, RHL, Jaipur, Rajasthan, India. E-mail: drsheetusingh1@gmail.com
Background: The aim of the study was to analyse data from the Indian centers participating in the Global Asthma Network (GAN) to find the current prevalence of asthmatic symptoms in children and adults. The trend of prevalence of asthma, and, treatment practices for asthma were also studied.
Methods: This was a questionnaire based, cross-sectional, multi-national study, where in responses from school going children in the age groups of 6–7 years, and 13–14 years, were analysed. Methodology and questionnaires were similar to the previous International study of asthma and allergies in Childhood (ISAAC).
Results: The number of subjects from the 9 Indian centers participating in GAN phase I were 20084, 25887, and 81296 in the 6–7-year-age group, 13–14-year-age group, and parents respectively. A prevalence of 3.16% in the 6-7-year age group, 3.63% in the 13-14-year-age group, and 3.30% in parents was noted for wheeze in the past 12 months. As compared to the ISAAC studies, the prevalence of current wheeze and trigger factorshad reduced (p<0.001). Clinical diagnosis of asthma was established in 18% of current wheezers and 30% of patients with severe asthma. Inhaled corticosteroid (ICS) use everyday was noted in less than 2.5% current wheezers and severe asthmatics. Daily ICS use was less than 1% when asthma was not clinically diagnosed.
Conclusion: As compared to previous studies, there was significant reduction in prevalence of symptoms of asthma and its causal factors. The study uncovers the problem of gross under diagnosis and under treatment in current wheezers in India.