Geographic information system-based mapping of air pollution & emergency room visits of patients for acute respiratory symptoms in Delhi, India (March 2018-February 2019)

Background & objectives: Studies assessing the spatial and temporal association of ambient air pollution with emergency room visits of patients having acute respiratory symptoms in Delhi are lacking. Therefore, the present study explored the relationship between spatio-temporal variation of particulate matter (PM)2.5 concentrations and air quality index (AQI) with emergency room (ER) visits of patients having acute respiratory symptoms in Delhi using the geographic information system (GIS) approach. Methods: The daily number of ER visits of patients having acute respiratory symptoms (less than or equal to two weeks) was recorded from the ER of four hospitals of Delhi from March 2018 to February 2019. Daily outdoor PM2.5 concentrations and air quality index (AQI) were obtained from the Delhi Pollution Control Committee. Spatial distribution of patients with acute respiratory symptoms visiting ER, PM2.5 concentrations and AQI were mapped for three seasons of Delhi using ArcGIS software. Results: Of the 70,594 patients screened from ER, 18,063 eligible patients were enrolled in the study. Winter days had poor AQI compared to moderate and satisfactory AQI during summer and monsoon days, respectively. None of the days reported good AQI (<50). During winters, an increase in acute respiratory ER visits of patients was associated with higher PM2.5 concentrations in the highly polluted northwest region of Delhi. In contrast, a lower number of acute respiratory ER visits of patients were seen from the ‘moderately polluted’ south-west region of Delhi with relatively lower PM2.5 concentrations. Interpretation & conclusions: Acute respiratory ER visits of patients were related to regional PM2.5 concentrations and AQI that differed during the three seasons of Delhi. The present study providessupport for identifying the hotspots and implementation of focused, intensive decentralized strategies to control ambient air pollution in worst-affected areas, in addition to the general city-wise strategies.

Molecular Signatures of MicroRNA in Obesity Associated Obstructive Sleep Apnea in Middle-Aged Adults

Objective: Obstructive sleep apnea (OSA) is a respiratory disorder with multiple clinical outcomes and is now being recognized as a serious health concern across the globe. However, the mechanisms of its pathophysiology are still elusive. Also, to date, evidence of miRNA regulation of sleep apnea in the Indian sub-population is unknown. Methods: In this study, we investigated the expression pattern of certain potential obesity-linked miRNAs in OSA subjects. Seventy adult subjects (20 obese OSA, 20 non-obese OSA and 30 healthy) were selected for this study. Total RNA was extracted and the expression of miR-21, miR-27, miR-29 and let-7 (normalized with internal control RNU48) was analyzed by SYBR Green-based qPCR. Results: We selected miR-21, miR-27, miR-29 and let-7 for their documented role in obesity. Relative miRNA expression profiles revealed differential expressions of all four above mentioned miRNAs in both obese and non-obese OSA subjects compared to healthy controls. Statistical analysis revealed a significant correlation between miRNA expression with obesity-associated parameters in OSA subjects. Conclusion: Our study demonstrates the involvement of four miRNAs (miR-21, miR-27, miR-29 and let-7) as potential molecular players of obesity-associated OSA. Identification of miRNA targets and in-depth analysis of their molecular mechanism in disease pathogenesis is further warranted.

Dual partial arc volumetric-modulated arc therapy: The game changer for accelerated hypofractionated whole-breast radiotherapy with simultaneous integrated tumor cavity boost in early breast cancer - A comparative dosimetric study with single partial arc volumetric-modulated arc therapy

Introduction: In a previous study, we demonstrated clinical and dosimetric feasibility of single partial arc volumetric modulated arc therapy (VMAT) for accelerated hypofractionated whole breast radiotherapy with simultaneous integrated boost (SIB) to lumpectomy cavity for early breast cancer. In this dosimetric study, we compared dual partial arcs versus single arc. Patients and Methods: Fifteen consecutive patients for treatment with hypofractionated accelerated radiotherapy with SIB using VMAT were planned with single partial arc in an earlier study, initial result of which is published elsewhere. The comparative dosimetric plan was created using two partial arcs. Skewness and kurtosis test, Paired Student's t-test, and Wilcoxon signed-rank test were applied for statistical analysis. P < 0.05 was considered statistically significant. Results: Most planning targets are better achieved with dual arc technique. Coverage of planning target volume (PTV) whole breast (PTVWB) and PTV lumpectomy cavity (PTVBOOST) was significantly improved with dual partial arc without significant difference in conformity index and homogeneity index. Dual arc improved dosimetric parameter significantly. Mean dose (Dmean) and maximum dose (Dmax) of whole breast PTV as well as Dmax of PTVBOOST; ipsilateral and contralateral lung Dmean, Dmax, 5 Gy volume (V5); contralateral lung Dmean, Dmax, V5; Heart V25 and V18; Dmean of 5 mm thickness skin; Dmean and Dmax of ribs; and Dmean and Dmax of contralateral breast were improved with dual arc. Conclusion: This is first of its kind study establishing the advantage of dual partial arcs in the current context. Dual partial arcs improved dosimetry over single partial arc. Significant dose reduction can be achieved for multiple crucial organs at risk

The time required to diagnose and treat lung cancer in Delhi, India: an updated experience of a public referral center

Background: Delays that postpone the evaluation and management of malignancy may lead to considerable morbidity. The primary objective of this study was to assess the time required to diagnose and treat lung cancer at an Indian public referral center that predominantly serves lower-income patients. Methods: A review of patients diagnosed with lung cancer between January 2008 and December 2016 was completed. We computed the median time intervals and inter-quartile ranges between symptom onset, definitive diagnostic investigation, confirmed histologic diagnosis, and chemotherapy initiation. Median intervals were correlated with baseline demographics and disease characteristics using Kruskal-Wallis test. Results: One thousand, three hundred and-seventy patients were selected. A majority (94.5%) with non-small cell lung cancer were diagnosed with advanced disease. After developing symptoms, patients required 101 [56­168] days to undergo a definitive diagnostic study, 107 [60­173] days to confirm a diagnosis, and 126 [85­196.8] days to initiate treatment. Patients who were previously treated for tuberculosis required more time to receive chemotherapy compared to those who were not (187 [134­261.5] days vs. 113 [75­180] days, p < 0.0001). A specialty Lung Cancer Clinic was implemented in 2012, and the mean referrals per month increased nearly four-fold (p < 0.0001), but the time required to administer treatment was not shortened. Conclusion: Among lower-income Indian patients, the most prominent delays occur prior to diagnosis. Efforts should be directed toward encouraging physicians to maintain a high index of clinical suspicion and educating patients to report concerning symptoms as early as possible.

Vascular Responses to Post Occlusive Reactive Hyperemia and Systemic Inflammation in Overlap Syndrome of Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea.

Background : Post-occlusive reactive hyperemia (RH) is impaired in Chronic Obstructive Pulmonary Disease (COPD) and Obstructive Sleep Apnea (OSA). The aim of the present study was to examine systemic vascular response and endothelial function in patients of Overlap Syndrome (OS) of COPD and OSA and also to investigate whether OS has any additional effect on endothelial dysfunction when compared to dysfunction caused by COPD alone. Methods : 31 COPD patients and 13 healthy controls participated in the study. Overnight Polysomnography was done to classify the patients into COPD only group (Apnea-Hypopnea Index <5) (n=15) and OS group (AHI >5) (n=16). Peripheral pulse waveform changes during reactive hyperemia were assessed using digital Photoplethysmography (PPG) technique in which pulse wave amplitude (PWA), Maximum slope of upstroke and Pulse Transit Time (PTT) were measured. C - reactive protein was assessed as marker of inflammation by ELISA. Results : Maximum percentage changes in PWA during RH were significantly lower in the both COPD group [20.34(12.02-34.07)] (p<0.001) and Overlap Syndrome group [10.96(6.21-21.49)] (p<0.0001) as compared to Controls [49.79(46.03-65.32)], whereas amplitude responses were not significantly different in the COPD and OS group (p>0.05). Maximum percentage change in slope of upstroke showed similar responses in the three groups. CRP levels (mg/l) were raised in COPD [11.60(1.75-15.00] (p<0.001) and OS group [12.52(5.28- 15.70))](p<0.0001) as compared to controls [0.59(0.58-0.91)]. Maximum percentage change in amplitude negatively correlated with serum CRP levels in COPD group (r=-0.557, p=0.03) and in OS group (r=-0.552, p= 0.02). FEV1% predicted positively correlated with maximum percentage change in amplitude in OS group

Evaluation of epidermal growth factor receptor mutations based on mutation specific immunohistochemistry in non-small cell lung cancer: A preliminary study.

Background & objectives: Studies have shown that immunohistochemical (IHC) staining using epidermal growth factor receptor (EGFR) mutation specific antibodies, is an easy and cost-effective, screening method compared with molecular techniques. The purpose of present study was to assess the percentage positivity of IHC using EGFR mutation specific antibodies in lung biopsy samples from patients with primary lung adenocarcinoma (ADC). Methods: Two hundred and six biopsies of primary lung ADC were subjected to EGFR mutation specific antibodies against del E746-A750 and L858R. Detection of EGFR mutation done by high resolution melting analysis (HRM) was used as gold standard. A concordance was established between molecular and IHC results. Frequency of IHC positivity was assessed. Results: Of the 206 patients, 129 were male and 77 were female patients, with a mean age of 54.1 yr. Fifty five (26.6%) patients (36 men; 19 women) showed positivity for IHC of del E746-A750 (33) and L858R (22). HRM results were available in 14 patients which showed EGFR mutations in correspondence with del E746-750 or L858R in 64.2 per cent cases. Positive cases on HRM were further confirmed by DNA sequencing and fragment analysis. Three patients showed exon20 variation. Two cases were negative for mutation. The genotype of del E746-750 mutation was more common than L858R. A concordance was established between molecular mutation and IHC in 85.7 per cent cases. Interpretation & conclusions: In this preliminary study from India mutation specific IHC was used for assessment of mutation status of EGFR. Although the number tested was small, a good concordance was observed between molecular EGFR mutation and IHC expression. IHC methodology is a potentially useful tool to guide clinicians for personalized treatment in lung ADC, especially where facilities for molecular analysis are not readily available and for use in small biopsies where material is scant for molecular tests.

Impaired systemic vascular reactivity & raised high-sensitivity C reactive protein levels in chronic obstructive pulmonary disease.

Background & objectives: Chronic obstructive pulmonary disease (COPD) is characterized by slowly progressive airflow limitaion, chronic lung inflammation and associated systemic manifestations. The objective of this preliminary study was to investigate the levels of high sensitivity C reactive protein (hs CRP) and tumour necrosis factor-α (TNF-α) as markers of systemic inflammation and assessment of systemic vascular reactivity that may play an important role in development of cardiovascular disease in COPD patients. Methods: Systemic vascular reactivity was assessed non-invasively by measuring peripheral pulse waveform changes during reactive hyperemia (RH) in 16 COPD patients and 14 controls by photoplethysmography technique (PPG). Parameters measured were pulse wave amplitude (PWA), slope and pulse transit time (PTT). Tumour necrosis factor-α (TNF-α) and hs CRP were measured as markers of inflammation. Results: PWA during the 1st, 2nd and 3rd minutes post release of occlusion were significantly higher than the baseline means in controls, whereas in the patient group there was no significant change in the PWA during any of the observed time periods following release of occlusion, in comparison to the baseline means. Similar results were observed in slope values for patients and controls. Maximum percentage change in PWA during RH with reference to baseline was significantly lower in patients as compared to controls (26.78±20.19 vs 57.20±19.80%, P<0.001). Maximum percentage change in slope during RH with reference to baseline was significantly lower in patients as compared to controls (19.77±10.73 vs 39.25±13.49%, P<0.001). A vascular tone response as represented by PTT was also impaired in the 3rd minute of RH as compared to baseline mean values in COPD patients only. Interpretation & conclusions: Our findings showed raised hs CRP levels and impaired systemic vascular reactivity in COPD patients. Whether these may increase the risk of cardiovascular disease in COPD patients need to be confirmed in future studies with large sample size and appropriate study design.

Pulse cyclophosphamide therapy in the management of patients with macular serpiginous choroidopathy.

Purpose: To evaluate safety and efficacy of intravenous pulse cyclophosphamide (CyP) in acute macular serpiginous choroiditis (SC). Methods: Patients with acute macular SC with lesions threatening and/ or involving fovea were enrolled. All patients received CyP (1 g/m2) for 3 days followed by high‑dose oral steroids (1.5 mg/kg) tapered over 6 months and monitored for visual acuity, response to treatment and systemic side effects. Results: Eight patients (seven unilateral and one bilateral) with median age of 27 years (range: 13-40 years) were recruited. Mean visual acuity at presentation was 0.71 ± 0.35 logarithm of the minimum angle of resolution while postpulse visual acuity was 0.40 ± 0.32. Final mean visual acuity at 1‑year was 0.31 ± 0.23 (P ≤ 0.05). Three eyes had recurrence and 3 patients developed transient hair loss with no other adverse effect. Conclusion: Intravenous CyP provides rapid resolution of lesion activity and thereby helps in maintaining good functional acuity.

Tracheobronchopathia osteochondroplastica: A rare cause of difficult intubation.

Tracheobronchopathia osteochondroplastica is a rare benign airway disorder which is characterised by submucosal nodules projecting into the tracheo-bronchial lumen usually involving the cartilaginous portions of the tracheo-bronchial tree or larynx. The condition is usually asymptomatic but can rarely present with difficulty during endotracheal intubation or rarely with obstructive airway complications. Bronchoscopic appearance is usually sufficient to make the diagnosis, and tissue biopsies are seldom required. No specific treatment is required in asymptomatic patients. However, interventional bronchoscopy procedures or surgery may be helpful in symptomatic cases.

Effect of Progressive Resistance Exercise Training on Hepatic Fat in Asian Indians with Non-Alcoholic Fatty Liver Disease.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance and lifestyle measures form the cornerstone of therapy. Objective: To study the effect of progressive resistance training (PRT) on hepatic fat content, body composition and insulin sensitivity in patients with NAFLD. Methods: This study included 24 adult patients with NAFLD diagnosed on ultrasonography. Subjects with alcohol intake >140 gm/week and any secondary cause of fatty liver were excluded. Patients underwent thrice weekly sessions (40 minutes each) of resistance exercises including flexion at biceps, triceps, and hip flexion, knee extension and heel rise for 12 weeks. Pre- and post-intervention evaluation included anthropometry, BIA analysis, short insulin tolerance test (SITT), lipid profile and hepatic fat quantification by MRI. Results: Twenty four patients (17 males, 7 females, mean age 39.8±10.5 yrs) completed the study protocol with 78.7% compliance to PRT protocol. There was significant decrease in waist, hip and mid-thigh circumferences and skinfold thicknesses at biceps, triceps, subscapular and suprailiac regions (p<0.05), with no significant change in BMI and WHR. Insulin sensitivity improved significantly at 12 weeks as indicated by increase in k-value (rate of change of glucose) on SITT (0.84 vs 1.3, p=0.002). A decrease in total cholesterol and LDL-c with increase in HDL-c was noted after 12 weeks (p<0.05). Hepatic fat content also decreased at 12 weeks (22.3±3.9 vs 21.4±4.0 %, p=0.01). Conclusion: Moderate intensity PRT is associated with significant improvement in hepatic fat, truncal subcutaneous fat and insulin sensitivity in patients with NAFLD.

Effects of seasonal variation on hospitalisations for acute exacerbations of chronic obstructive pulmonary disease.

Objective. To identify seasonal differences in the frequency and outcome of hospital admissions due to acute exacerbation of chronic obstructive pulmonary disease (AE-COPD). Method. A cohort study with data from 94 admissions due to AE-COPD at a tertiary care hospital in New Delhi, during the period 1995-1997. Results. The sample consisted of 94 patients (21.3% females) with a mean age of 61.2 years. There were an average of 7.8 admissions per month during the year. After a trough in November (two admissions/month), there was a sharp rise in admissions which peaked in February (15 admissions/month). Overall, there was no statistically significant difference in admissions per month in winter season (November-February) versus summer season (March-October) (p=0.251.) We did not identify significant seasonal differences in patients' demographics, laboratory results including arterial blood gases, mortality, duration of stay, requirement of invasive mechanical ventilation, or intensive care unit (ICU). Conclusions. There was no association between the season of the year and the frequency of hospitalisation or outcome due to AE-COPD. However, there are dramatic increases in the frequency of admissions starting in November and peaking in February of the following year.

Study of dihydropteroate synthase (DHPS) gene mutations among isolates of Pneumocystis jiroveci.

BACKGROUND & OBJECTIVES: Pneumocystis jiroveci (also known as P. carinii) causes fatal pneumonia in patients with AIDS and other immunocompromised patients. Co-trimoxazole (trimethoprim + sulphamethoxazole, TMP-SMZ) is the drug of choice for treatment and prophylaxis. Widespread use of sulpha medication has raised the possible selection of resistant P. jiroveci strains worldwide. Non-synonymous polymorphisms associated with sulpha resistance have been observed in P. jiroveci dihydropteroate synthase (DHPS) gene at codons 55 and 57. In view of this, we investigated mutation at DHPS locus amongst P. jiroveci isolates obtained at a tertiary care hospital in north India. METHODS: Microscopic examination of P. jiroveci in 69 clinical samples obtained from patients suspected to have P. carinii pneumonia (PCP), was performed by Grocott's Gomori methenamine silver and direct fluorescent antibody staining. Molecular studies were carried out by polymerase chain reaction (PCR) using major surface glycoprotein (MSG) as the target gene. Investigations for DHPS mutations were carried at specific 55th and 57th codon using PCR-RFLP (restriction fragment length polymorphism) assay. RESULTS: Microscopic examination detected P. jiroveci in four cases and MSG gene was amplified in five cases. Further, amplification of DHPS gene was successful in four of the five cases positive by MSG gene PCR. No point mutation was observed and all four isolates presented wild-type sequences at DHPS gene by RFLP analysis. INTERPRETATION & CONCLUSION: Although our findings suggest that in Indian subpopulation, point mutations in DHPS gene of P. jiroveci are not as common as in other parts of the developed world, further studies are needed.

Use of different primer directed sequence amplification by polymerase chain reaction for identification of Pneumocystis jirovecii in clinical samples.

BACKGROUND: Pneumocystis carinii pneumonia (PCP), caused by opportunistic agent Pneumocystis jirovecii (formerly, Pneumocystis carinii is one of the most serious respiratory infection in immunocompromised patients. AIM: The present study was conducted to compare polymerase chain reaction (PCR) assays targetting three different genes of Pneumocystis to study their application in its diagnosis. METHODS: One hundred and eighty (n = 180) clinical samples from 145 immunocompromised patients with clinical suspicion of PCP and 35 samples from control group of 30 immunocompetent individuals with respiratory infections other than PCP were prospectively examined for the presence of Pneumocystis jirovecii (P. jirovecii). All the samples were subjected to microscopic examination, one single [major surface glycoprotein, (MSG)] and two nested [mitochondrial large subunit ribosomal ribonucelic acid, (mtLSU rRNA) and internal transcribed spacer (ITS) region], polymerase chain reaction assays. RESULTS: Microscopic examination was positive in only six (n = 6) patients, whereas single round MSG PCR detected P. jirovecii deoxyribonucleic acid (DNA) in 16 cases. When the clinical samples were tested by mtLSU rRNA and ITS nested PCR assays, it was possible to detect seven additional cases of PCP, making it to a total of 23 cases. None of the clinical specimens in control group (n = 30) were positive by any of the above-mentioned techniques. Amongst the 81 bronchoalveolar lavage (BAL) samples tested, 16 were positive by MSG PCR, while 20 were positive by both nested, i.e., mtLSU rRNA and ITS PCR assays. Similarly, out of 50 sputum samples, only three were positive by MSG, seven by mtLSU rRNA and six by ITS nested PCR assays. CONCLUSION: It has been observed that MSG is relatively more sensitive when single round PCR assay is used for detection of human Pneumocystosis compared to the first (single) rounds of either ITS or mtLSU rRNA nested PCRs. However, the two nested PCRs using ITS and mtLSU rRNA have been found to be more sensitive. On comparison of two nested PCR assays, the results have been more or less comparable.

Non-pharmacological management of hypertension.

Hypertension is a silent killer. Indians are racially predisposed to cardiovascular disease and the increasing burden of hypertension has only added to the problem. Economic constraints and the allure of additional benefits without adverse effects have made lifestyle modifications an attractive proposition in developing and developed countries alike. Blood pressure is a continuum and any increase above optimal confers additional independent risk of vascular disease, even in ranges previously considered normal. While antihypertensive agents have been used for those patients with blood pressure above the traditional cutoff, there has been increasing emphasis on the prevention and treatment of hypertension by non-pharmacological means, termed 'lifestyle modifications.' A MEDLINE search was done for relevant references with emphasis on original studies, randomized controlled trials and meta-analyses. Lifestyle modifications that effectively lower blood pressure are increased physical activity, weight loss, limited alcohol consumption, reduced sodium intake and the Dietary Approaches to Stop Hypertension diet. Lifestyle modification is recommended as initial therapy in stage 1 hypertension before initiation of drug therapy and as an adjunct to medication in persons already on drug therapy. In pre-hypertensives, it can reduce the incidence of hypertension and lower end-organ damage. It is emphasized that simple advice from physicians can have a positive influence on patients' motivation to make lifestyle changes.

Hypotension is a predictor of mortality in acute exacerbations of chronic obstructive pulmonary disease.

OBJECTIVES: To identify variables that predict the in-hospital course and prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: A retrospective analysis of 94 patients (20 females) with AECOPD. Twenty-one variables including arterial blood gas studies were analysed. RESULTS: The mean age was 61.2 years. The in-hospital mortality rate was 12.8%; 28.6% of patients required invasive mechanical ventilation and 37.2% required ICU care. In univariate analysis, aypotension at presentation (systolic blood-pressure < 90 mmHg) [p = 0.002, odds ratio OR 10.95, 95% confidence interval (CI) 1.90-63.00); central cyanosis (p = 0.007, OR 6.91, 95% CI 1.42-33.59); and cor-pulmonale (p = 0.009, OR 10.46, 95% CI 1.26-86.46) were univariately associated with in-hospital mortality. On multivariate analysis, hypotension (p = 0.049, OR 18.419, 95% CI 1.013-334.752) remained the only independent predictor. CONCLUSIONS: More than the markers of poor gas exchange, the presence of hypotension indicates a poor in-hospital prognosis in AECOPD.

Small cell lung cancer: an update on therapeutic aspects.

Small cell lung cancer comprises approximately 20% of all lung cancers and continues to be a difficult management issue. More than two-thirds of cases present with extensive disease, which has spread beyond the himithorax and regional ipsilateral nodes. While response rates to chemotherapy are relatively high, durable responses are rare, and long-term survival rates are anecdotal. Although many attempts have been made to develop new therapies, a combination of etoposide with either cisplatin or carboplatin remains the most widely used first-line therapy for extensive disease. For those with limited disease, chemotherapy with concomitant radiotherapy (given with the first or second cycles of chemotherapy) is considered the standard of care. Over the last decade, several new drugs and targeted agents have been identified with the aim to improve outcome of this malignancy. In this review we highlight recent developments in the management of this tumour.

Quality of life measures in lung cancer.

Lung cancer is one of the leading causes of cancer death worldwide. Survival has not improved significantly in spite of newer therapies. In view of the high-symptom burden and severe morbidity, evaluation of quality of life (QOL) becomes important in these patients. Several instruments are now available for this purpose, and have demonstrated good correlation with performance status, symptoms, and survival. Quality of life assessments also help in comparing different therapeutic regimes, thus allowing selection of the appropriate modality. Problems of inconsistent interpretability and high-patient dropout rate poses a challenging problem that needs to be tackled. In spite of these drawbacks, QOL is now considered to be an essential component of lung cancer management and should be performed routinely. Such a practice will help the physician plan appropriate treatment strategies and set practical therapeutic goals.