Screening for Lung Cancer in India: Expert Opinion Statement.

Lung cancer (LC) has the highest rate of disability-adjusted life years (DALY) of all cancers in India. A large majority of patients with LC present with advanced disease, resulting in poor survival rates. Early diagnosis can improve survival outcomes as the patients can be treated with curative intent. The National Lung Screening Trial (NLST), in 53,454 persons at high risk for LC in the US, showed a 20% (95% confidence interval of 6.8-26.7; p = 0.004) relative reduction in LC-specific mortality in the patients screened with low-dose computed tomography (LDCT) compared with chest X-ray. To date, India does not have a formal LC screening (LCS) program. As a panel of experts, we reviewed a synthesis of a targeted literature search on the burden of LC, the current status of diagnosis of LC, barriers to early diagnosis, current referral pathways, LC risk patterns, use of artificial intelligence (AI) and risk calculators for risk assessment, and a multidisciplinary team (MDT) approach to diagnosis LC. We used the existing international LCS guidelines, data from published literature, and clinical experience to depict the characteristics of the population at risk of LC in India-young age (<40 years), smoking, especially the predominance of bidi smoking (an indigenous form of tobacco smoking), exposure to biomass fuel smoke, especially in rural women, and air pollution being the prominent features. LC in India is characterized by a higher rate of driver mutations and adenocarcinomatous histology. Here, we present the expert opinion on risk-based LCS in India and discuss the challenges, facilitators, and research priorities for the effective rollout of LCS in India.

[68Ga]Ga-Pentixafor PET/CT imaging for in vivo CXCR4 receptor mapping in different lung cancer histologic sub-types: correlation with quantitative receptors' density by immunochemistry techniques.

PURPOSE: In vivo CXCR4 receptor quantification in different lung cancer (LC) sub-types using [68Ga]Ga-Pentixafor PET/CT and to study correlation with quantitative CXCR4 receptors' tissue density by immunochemistry analyses. METHODS: [68Ga]Ga-Pentixafor PET/CT imaging was performed prospectively in 94 (77 M: 17F, mean age 60.1 ± 10.1 years) LC patients. CXCR4 receptors' expression on lung mass in all the patients was estimated by immunohistochemistry (IHC) and fluorescence-activated cell sorting (FACS) analyses. SUVmax on PET, intensity score on IHC, and mean fluorescence index (MFI) on FACS analyses were measured. RESULTS: A total of 75/94 (79.8%) cases had non-small cell lung cancer (NSCLC), 14 (14.9%) had small cell lung cancer (SCLC), and 5 (5.3%) had lung neuroendocrine neoplasm (NEN). All LC types showed increased CXCR4 expression on PET (SUVmax) and FACS (MFI). However, both these parameters (mean SUVmax = 10.3 ± 5.0; mean MFI = 349.0 ± 99.0) were significantly (p = 0.005) higher in SCLC as compared to those in NSCLC and lung NEN. The mean SUVmax in adenocarcinoma (n = 16) was 8.0 ± 1.9 which was significantly (p = 0.003) higher than in squamous cell carcinoma (n = 54; 6.2 ± 2.1) and in not-otherwise specified (NOS) sub-types (n = 5; 5.8 ± 1.5) of NSCLC. A significant correlation (r = 0.697; p = 001) was seen between SUVmax and MFI values in squamous cell NSCLC as well as in NSCLC adenocarcinoma (r = 0.538, p = 0.031) which supports the specific in vivo uptake of [68Ga]Ga-Pentixafor by CXCR4 receptors. However, this correlation was not significant in SCLC (r = 0.435, p = 0.121) and NEN (r = 0.747, p = 0.147) which may be due to the small sample size. [68Ga]Ga-Pentixafor PET/CT provided good sensitivity (85.7%) and specificity (78.1%) for differentiating SCLC from NSCLC (ROC cutoff SUVmax = 7.2). This technique presented similar sensitivity (87.5%) and specificity (71.4%) (ROC cutoff SUVmax = 6.7) for differentiating adenocarcinoma and squamous cell variants of NSCLC. CONCLUSION: The high sensitivity and specificity of [68Ga]Ga-Pentixafor PET/CT for in vivo targeting of CXCR4 receptors in lung cancer can thus be used effectively for the response assessment and development of CXCR4-based radioligand therapies in LC.

A study on the effect of mobile phone use on sleep.

Background & objectives: Several studies have been conducted globally to assess the impact of usage of mobile phones on quality and duration of sleep as also on day time sleepiness. The objective of the present study was to assess the effect of mobile phone usage on the quality and composition of sleep in a sample from Indian population. Methods: The study was conducted at two tertiary care hospitals in north India from July 2014 to September 2019. A total of 566 participants were recruited in this study from both the centres. Sleep quality was assessed with the help of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Subsequently, actigraphy was done in 96 participants and polysomnography in 95 participants. Results: Of the 566 participants, 128 (22.61%) had PSQI ≥5, reflecting poor sleep quality. A higher use of mobile phone was significantly associated with a poor sleep quality as a component of PSQI questionnaire (P=0.01) and higher overall PSQI score (P=0.01). The latency from sleep onset to N2 and N3 sleep stages was significantly shorter in participants having a higher mobile phone usage as compared to those with a lower usage [Median (range): 13.5 min (1.5-109) vs. 6.5 min (0-89); P=0.02] and [Median (range): 49 min (8.5-220.5) vs. 28.75 min (0-141); P=0.03], respectively. Interpretation & conclusions: This study focused on the maladaptive changes brought on by mobile phone usage on sleep. More studies with larger sample sizes need to be done that may serve to confirm the hypothesis generating findings of our study.

Prevalence of Antineutrophil Cytoplasmic Antibodies and Antinuclear Antibodies in Patients with Pulmonary Tuberculosis: A Tertiary Care Center Experience from North India.

BACKGROUND: Tuberculosis (TB) can have manifestations closely mimicking autoimmune diseases. The prevalence of autoantibodies in TB varies among different populations. OBJECTIVES: To study the prevalence of anti-neutrophilic cytoplasmic antibodies (ANCA) and antinuclear antibodies (ANA) in pulmonary tuberculosis (PTB). METHODS: This was a cross-sectional, observational study. Subjects with microbiologically confirmed PTB, either via smear or culture positivity on sputum or bronchoalveolar lavage (BAL) fluid, or positive rapid diagnostic tests were included. ANCA against proteinase-3 (PR3), myeloperoxidase (MPO), lactoferrin, and elastase were tested using an enzyme-linked immunosorbent assay (ELISA). ANA was detected using indirect immunofluorescence (IIF). RESULTS: Eighty-nine subjects with a median [interquartile range (IQR)] age of 28 (20-46) years, 67.4% males, were recruited. Eighty-one subjects had microbiological confirmation on sputum examination, and eight required examination of BAL fluid. Sera were drawn from 62 treatment-naïve subjects, the rest (27) were on antitubercular therapy (ATT). Eighty-six (96.6%) subjects tested positive for anti-elastase antibody, seven of which were also positive for anti-PR3. None were positive for anti-MPO and anti-lactoferrin. Six (6.7%) subjects tested positive for ANA. None of the subjects had features of underlying connective tissue disease or vasculitis. CONCLUSION: PTB patients showed a high prevalence of anti-elastase and a low prevalence of ANA and anti-PR3 antibodies. ANCA positivity should be interpreted with caution in TB endemic areas. The role of anti-elastase antibodies in differentiating TB from ANCA-associated vasculitis (AAV) needs further research.

Long-term Survival and Quality of Life among Survivors Discharged from a Respiratory ICU in North India: A Prospective Study.

Background: Advancements in the intensive care unit (ICU) have improved critically ill subjects' short-term outcomes. However, there is a need to understand the long-term outcomes of these subjects. Herein, we study the long-term outcomes and factors associated with poor outcomes in critically ill subjects with medical illnesses. Materials and methods: All subjects (≥12 years) discharged after an ICU stay of at least 48 hours were included. We evaluated the subjects at 3 and 6 months after ICU discharge. At each visit, subjects were administered the World Health Organization Quality of Life Instrument (WHO-QOL-BREF) questionnaire. The primary outcome was mortality at 6 months after ICU discharge. The key secondary outcome was quality of life (QOL) at 6 months. Results: In total, 265 subjects were admitted to the ICU, of whom 53 subjects (20%) died in the ICU, and 54 were excluded. Finally, 158 subjects were included: 10 (6.3%) subjects were lost to follow-up. The mortality at 6 months was 17.7% (28/158). Most subjects [16.5% (26/158)] died within the initial 3 months after ICU discharge. Quality of life scores were low in all the domains of WHO-QOL-BREF. About 12% (n = 14) of subjects could not perform the activity of daily living at 6 months. After adjusting for covariates, ICU-acquired weakness at the time of discharge (OR 15.12; 95% CI, 2.08-109.81, p <0.01) and requirement for home ventilation (OR 22; 95% CI, 3.1-155, p <0.01) were associated with mortality at 6 months. Conclusion: Intensive care unit survivors have a high risk of death and a poor QOL during the initial 6 months following discharge. How to cite this article: Kodati R, Muthu V, Agarwal R, Dhooria S, Aggarwal AN, Prasad KT, et al. Long-term Survival and Quality of Life among Survivors Discharged from a Respiratory ICU in North India: A Prospective Study. Indian J Crit Care Med 2022;26(10):1078-1085.

UGT1A1 Gene Polymorphisms in Patients with Small Cell Lung Cancer Treated with Irinotecan-Platinum Doublet Chemotherapy and Their Association with Gastrointestinal Toxicity and Overall Survival.

BACKGROUND: Irinotecan (CPT11) is an important drug for small cell lung cancer (SCLC) chemotherapy (CTx). UDP-glucuronosyltransferase 1A1 (UGT1A1) polymorphisms can influence CPT11-related toxicity. This study aimed to assess prevalence of UGT1A1 polymorphisms and their association with clinical outcomes in patients with SCLC on CPT11-CTx. METHODS: An observational cohort of treatment-naïve patients with SCLC was given CPT11-platinum doublet at a referral center in North India over 3 years. Clinical outcomes assessed were hematological and gastrointestinal toxicity (Common Terminology Criteria for Adverse Events, version 3.0), response rates (RECIST), and overall survival (OS). Peripheral blood was drawn from all enrolled patients just prior to CPT11-CTx initiation, and genomic DNA was isolated. Genotyping was done by polymerase chain reaction (PCR)-restriction fragment length polymorphism for UGT1A1*7, UGT1A1*6, and UGT1A1*27 and by PCR-DNA sequencing for UGT1A1*28. Patients were classified as homozygous wild-type (WT/WT), heterozygous mutant (WT/M), or homozygous mutant (M/M) for each polymorphism assessed. RESULTS: Of 140 patients enrolled, no mutant alleles were found for UGT1A1*27 or UGT1A1*7. Frequency of UGT1A1*6 polymorphisms (n = 111) was 89.2% for WT/WT, 8.1% for WT/M, and 2.7% for M/M. For UGT1A1*28 (n = 102), this was 41.2% for WT/WT, 43.1% for WT/M, and 15.7% for M/M. UGT1A1*6 WT/WT patients tolerated >95% predicted CPT11 dose more frequently (59.6% vs. 25.0% in WT/M-M/M combined group; p = .026). The UGT1A1*6 WT/M-M/M group also experienced severe (grade ≥3) diarrhea (41.7% vs. 17.2% in WT/WT; p = .044) and mucositis (41.7% vs. 8.1% in WT/WT; p = .005) more frequently. On multivariate logistic regression analysis, UGT1A1*6 WT/M-M/M status was the only variable associated with occurrence of both mucositis (odds ratio [OR], 10.4) and severe diarrhea (OR, 4.8). UGT1A1*28 WT/M-M/M patients had better OS (320 days [95% confidence interval, 203-437] vs. 216 days [95% confidence interval, 140-292] in WT/WT group; p = .047). On multivariate Cox proportional hazards analysis, UGT1A1*28 WT/M-M/M status was independently associated with better OS (hazard ratio, 0.35), whereas lack of objective radiological response, moderate/heavy smoking, and increasing age were associated with worse OS. CONCLUSION: UGT1A1*6 and UGT1A1*28 polymorphisms were associated with increased gastrointestinal toxicity and improved OS, respectively, in North Indian patients with SCLC receiving CPT11-CTx. IMPLICATIONS FOR PRACTICE: UGT1A1 gene polymorphisms are known to influence irinotecan-related toxicity. In this prospective cohort study of patients with small cell lung cancer receiving first-line irinotecan-platinum chemotherapy, the prevalence of UGT1A1*6 polymorphisms was found to be 10.8% UGT1A1*6 and 58.8% UGT1A1*28 homo/heterozygous mutant, respectively. UGT1A1*6 homo/heterozygous mutant status was associated with severe diarrhea and mucositis. UGT1A1*28 homo/heterozygous mutant status was independently associated with improved overall survival.

Timing of folic acid/vitamin B12 supplementation and hematologic toxicity during first-line treatment of patients with nonsquamous non-small cell lung cancer using pemetrexed-based chemotherapy: The PEMVITASTART randomized trial.

BACKGROUND: Vitamin B12 and folic acid (FA) supplementation (B12-FAS) reduces hematologic toxicity with pemetrexed-based chemotherapy (PEM). However, the basis for recommending 1 week of B12-FAS before PEM initiation has never been proven in a randomized trial. METHODS: An open-label, randomized trial (PEMVITASTART; clinicaltrials.gov identifier NCT02679443) was conducted to compare hematologic toxicity between patients with locally advanced/metastatic nonsquamous non-small cell lung cancer who initiated PEM after 5 to 7 days of B12-FAS (delayed arm [DA]) versus those who received B12-FAS simultaneously (≤24 hours) with PEM initiation (immediate arm [IA]). Every 3 weeks, all enrolled patients received pemetrexed (500 mg/m2 ) AND either cisplatin (65 mg/m2 ) OR carboplatin (area under the curve = 5.0 mg/mL per minute) on day 1 for a maximum of 6 cycles. Supplementation consisted of oral FA 1000 µg daily and intramuscular vitamin B12 1000 µg every 3 weeks. The primary outcome was any grade of hematologic toxicity and secondary outcomes included grade 3/4 hematologic toxicity, the relative dose intensity delivered, and changes in serum levels of B12/FA/homocysteine. RESULTS: Of 161 patients (IA, n = 81; DA, n = 80) recruited, 150 (IA, n = 77; DA, n = 73) received ≥1 cycle and were included in a modified intention-to-treat analysis. Baseline anemia prevalence was 34.7% (IA, 32.5%; DA, 37%; P = .56). The incidence of any grade anemia, leukopenia, neutropenia, and thrombocytopenia was 87% versus 87.7% (P = .90), 37.7% versus 28.8% (P = .25), 20.8% versus 15.1% (P = .36), and 31.2% versus 16.4% (P = .04), respectively, in the IA and DA, respectively. Grade 3/4 cytopenias and median relative dose intensities delivered (pemetrexed, 93.5%; platinum, 91%) were similar in both arms. After cycle 3 (compared with baseline), serum homocysteine levels were lower, whereas FA and B12 levels were higher. In the DA, serum FA and B12 levels on day 1 of cycle 1 (after 5-7 days of B12-FAS) were significantly higher than at baseline, but homocysteine levels were similar. CONCLUSIONS: Simultaneous B12-FAS initiation with a pemetrexed-platinum doublet chemotherapy regimen is feasible and does not lead to enhanced hematologic toxicity. Serum homocysteine levels are unaffected by 5 to 7 days of B12-FAS.

Prevalence of sensitization to Aspergillus flavus in patients with allergic bronchopulmonary aspergillosis.

Aspergillus fumigatus is the most common Aspergillus species worldwide; however, A. flavus has also been shown to be prevalent in North India. Herein, we investigate the prevalence of sensitization to A. flavus in subjects with allergic bronchopulmonary aspergillosis (ABPA). We also evaluate the occurrence of allergic bronchopulmonary mycosis (ABPM) due to A. flavus. Treatment-naive subjects with ABPA underwent sputum culture; and, skin testing, fungal-specific immunoglobulin E (IgE) and serum precipitation tests for A. fumigatus and A. flavus. Sensitization to A. flavus was diagnosed if any immunological test for A. flavus was positive in subjects with ABPA. ABPM was labelled as probable if sputum cultures grew A. flavus and A. flavus-specific IgE was greater than A. fumigatus-specific IgE; and, possible if only A. flavus-specific IgE was greater than A. fumigatus-specific IgE. Fifty-three subjects with a mean (SD) age of 34.2 (12.8) years were included. Sensitization to A. flavus was seen in 51 (96.2%) subjects, with overlap occurring in 49 (92.5%), 21 (39.6%), and 12 (22.6%) instances on fungal-specific IgE, skin prick test and precipitins, respectively. Sputum culture was positive in 18 (33.9%; A. flavus [n = 12], A. fumigatus [n = 6]) subjects. ABPM due to A. flavus was diagnosed in 16 (30.2%) subjects (10 probable, 6 possible). They were more likely to have high-attenuation mucus and a trend towards higher occurrence of sinusitis, compared to ABPA. We found a high occurrence of sensitization to A. flavus in subjects with ABPA. Subjects with A. flavus-related ABPM had a higher likelihood of high-attenuation mucus and probability of sinusitis. More studies are required to confirm this observation.

XRCC1 632 as a candidate for cancer predisposition via a complex interaction with genetic variants of base excision repair and double strand break repair genes.

Aim: The DNA repair system safeguards integrity of DNA. Genetic alterations force the improper repair which in conjugation with other factors ultimately results in carcinogenesis. Materials & methods: PCR-restriction fragment length polymorphism was used for genotyping, which was followed by statistical analysis using logistic regression analysis, multifactor dimensionality reduction and classification and regression analysis tree, elaborating the association with lung cancer subjects. Results: Combination of XRCC1 632 and OGG1326 showcased a high risk of eightfold (odds ratio: 7.92; 95% CI: 2.68-23.4; p = 0.0002; false discovery rate (FDR) p = 0.002). Similarly, XRCC1 632 and MUTYH 324 (odds ratio: 5.07; 95% CI: 2.6-9.67; p < 0.0001; FDRp = 0.002) had a high risk. Multifactor dimensionality reduction analysis revealed five factor model as the best model with prediction error of 0.37 (p = 0.02). Conclusion: There was a clear indication that high order interactions were major role players in the study.

XPG polymorphisms and their association with lung cancer susceptibility, overall survival and response in North Indian patients treated with platinum-based doublet chemotherapy.

AIM: The study investigates association of XPG polymorphism with lung cancer susceptibility, overall survival and clinical outcomes in North Indian population. RESULTS: A significant protective effect was observed for 2228959 C/A polymorphism with lung cancer and its histological subtypes. An increased hazard ratio (HR) was observed in 17655 G/C variant among small-cell lung carcinoma patients with mutant genotype (HR: 2.55; p = 0.05). Individuals treated with irinotecan-cisplatin/carboplatin regimen showed a longer survival time (HR1: 0.04; median survival time [MST]: 32.5 months). Subjects treated with pemetrexed-cisplatin/carboplain regimen were associated with higher mortality rate in lung cancer patients (HR1: 1.83;  MST: 9.13 months). CONCLUSION: 2228959 C/A polymorphism contributes to protective effect in lung cancer patients. 2228959 C/A polymorphism might be associated with favorable prognosis in lung cancer risk.

Role of polymorphic XRCC6 (Ku70)/XRCC7 (DNA-PKcs) genes towards susceptibility and prognosis of lung cancer patients undergoing platinum based doublet chemotherapy.

The DNA repair genes XRCC6 and XRCC7 formed an integral part of double strand break repair (DSBR) pathway. The two genes are thought to play an important role in the repair of lethal double strand damage on DNA. Polymorphic DSBR genes are studied to effect genomic stability. We intend to explore the association of DSBR genes i.e. XRCC6 and XRCC7 with susceptibility and survival in North Indian lung cancer patients. DNA isolation and genotyping was done for 320 controls and 330 lung cancer cases enrolled in the study. Each and every lung cancer study subjects were made a telephonic call and were followed for their health after administration of chemotherapy. Statistical analysis for susceptibility was done using logistic regression analysis. Survival analysis was done using Kaplan-Meier followed by Cox-regression. Small cell lung cancer (SCLC) subtype posed an amplified risk towards lung cancer in case of XRCC7 6721G>T (OR = 4.11, p = 0.0040). Gene-environment interaction analysis revealed that non-smokers with heterozygous genotype (CG) in case of XRCC6 61C>G showed a strong protective effect (OR = 0.38, p = 0.01) towards lung cancer. Survival analysis revealed poor prognosis in case of XRCC6 61C>G SCLC subtype. XRCC6 and XRCC7 were not involved in overall susceptibility and survival. However, in case of XRCC7 6721G>T subjects with SCLC subtype showed an increased susceptibility while poor prognosis in case of XRCC6 61C>G.

Utility of the revised Edmonton Symptom Assessment System (ESAS-r) and the Patient-Reported Functional Status (PRFS) in lung cancer patients.

BACKGROUND: Symptom palliation is an important objective of treatment in advanced/metastatic lung cancer (LC). Significant psychological, minor physical symptoms and several social/emotional issues often go unnoticed. This prospective study aimed to evaluate utility of patients' perspectives [self-reported symptom assessment by revised Edmonton Symptom Assessment System (ESAS-r) and self-reported functional status by Patient-Reported Functional Status (PRFS)] amongst LC patients undergoing chemotherapy. METHODS: Consecutive newly diagnosed treatment-naïve LC patients attending a tertiary referral center in North India from January 2014 to March 2015 were included. All patients received standard histology-guided platinum-doublet chemotherapy. ESAS-r and PRFS questionnaires were administered under guidance, once at the time of initial assessment/diagnosis, repeated at start of chemotherapy, before C4, and after completion of chemotherapy (end of chemotherapy (EOCTx)). Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire was also administered. Baseline and post-treatment scores were compared. RESULTS: Majority of 133 patients enrolled were males (86.5%,n = 115), were current/ex-smokers (81.2%, n = 108), had advanced stage [IIIB = 30.1% (n = 40), IV = 52.6% (n = 70)], and were of non-small-cell type (NSCLC;84.2%,n = 112). On baseline ESAS-r, the highest mean symptom scores were observed for tiredness followed by anorexia. Mean ESAS-r scores before C4 as well as at EOCTX were significantly better than baseline ESAS-r scores in all its components except nausea. Similarly, PRFS before C4 and EOCTx was significantly improved compared to baseline. However, Karnofsky Performance Scale (KPS) and Eastern Cooperative Oncology Group Performance Status assessed at baseline did not show significant improvement at treatment completion. FACT-L score at EOCTx showed significant improvement from baseline in physical and functional well-being domains but not for social/family and emotional well-being domains. CONCLUSION: This study validated utility of ESAS-r and PRFS in Indian LC patients. These instruments should be used in routine clinical practice besides physicians' assessment of PS (KPS/ECOG).

Role of Sequence Variations in AhR Gene Towards Modulating Smoking Induced Lung Cancer Susceptibility in North Indian Population: A Multiple Interaction Analysis.

BACKGROUND: AhR, a ubiquitously expressed ligand-activated transcription factor, upon its encounter with the foreign ligands activates the transcriptional machinery of genes encoding for bio-transformation enzymes like CYP1A1 hence, mediating the metabolism of Poly aromatic hydrocarbons and nitrosamines which account for the maximally found carcinogen in cigarette smoke. Polymorphic variants of AhR play a significant role and are held responsible for disposing the individuals with greater chances of acquiring lung cancer. OBJECTIVE: To study the role of AhR variants (rs2282885, rs10250822, rs7811989, rs2066853) in affect-ing lung cancer susceptibility. METHODS: 297 cases and 320 controls have been genotyped using PCR-RFLP technique. In order to find out the association, unconditional logistic regression approach was used. To analyze high order in-teractions Multifactor Dimensionality Reduction and Classification and regression tree was used. RESULTS: Subjects carrying the variant genotype for AhR rs7811989 showed a two-fold risk (p=0.007) and a marginal risk was also seen in case of individuals carrying either single or double copy of suscep-tible allele for rs102550822 (p=0.02). Whereas the variant allele for rs2066853 showcased a strong pro-tective effect (p=0.003). SQCC individuals with mutant genotype of rs2066853 also exhibited a protec-tive effect towards lung cancer (OR=0.30, p=0.0013). The association of rs7811989 mutant genotype and rs10250822 mutant genotype was evident especially in smokers as compared to non-smokers. AhR rs2066853 showed a decreased risk in smokers with mutant genotype (p=0.002). MDR approach gave the best interaction model of AhR rs2066853 and smoking (CVC=10/10, prediction error=0.42). CONCLUSION: AhR polymorphic variations can significantly contribute towards lung cancer predisposi-tion.

Vitamin D levels in asthmatic patients with and without allergic bronchopulmonary aspergillosis.

Vitamin D deficiency is believed to be a pathogenetic factor in patients with allergic bronchopulmonary aspergillosis (ABPA) and cystic fibrosis. Whether vitamin D deficiency is also prevalent in ABPA complicating asthma, remains unknown. Herein, we evaluated vitamin D levels in asthmatic patients with and without ABPA. In a prospective study, plasma vitamin D (25[OH]D) levels were measured in consecutive subjects with asthma (n = 75), ABPA (n = 158) and healthy volunteers (n = 50). Vitamin D levels <20 ng/mL were considered as vitamin D deficiency. There was no difference in mean (95% CI) vitamin D levels between healthy controls (15.3 [12.7-17.9]), asthmatics (19.2 [16.3-22.1]) and subjects with ABPA (18.9 [16.9-20.8]) (P = .22). Vitamin D deficiency was encountered in 70%, 64% and 65% of the healthy controls, asthmatics and ABPA subjects, respectively, and was not different between the groups (P = .79). There was no difference in the asthma control, pulmonary function, immunological findings and the severity of bronchiectasis, in patients with ABPA, with and without vitamin D deficiency. Vitamin D deficiency is equally prevalent in asthmatic patients with or without ABPA in the Indian subcontinent, and does not appear to play a major role in the pathogenesis of ABPA complicating asthma.

Association of XPA Polymorphisms Towards Lung Cancer Susceptibility and its Predictive Role in Overall Survival of North Indians.

The present study investigated the role of Xeroderma pigmentosum group A (XPA) polymorphism (A23G and G709A) with lung cancer risk and its association with overall survival in North Indians. 370 cases and 370 controls were investigated to evaluate association between XPA polymorphism (A23G and G709A) with lung cancer risk using logistic regression analysis. A follow-up study was also conducted for 291 lung cancer cases illustrating correlation between overall survival in lung cancer patients and XPA variants. GG genotype showed an increased lung cancer risk (p = 0.0007) for A23G polymorphism whereas G709A polymorphism was associated with significant protective effect in heterozygous (AG) subjects (p = 0.001). When stratified according to smoking status an increased risk for lung cancer was observed for GG genotype in A23G polymorphism (p = 0.0002). A poor survival in females carrying variant genotype (GG) was observed (p = 0.001; MST = 4.16 months) for A23G polymorphism. Adenocarcinoma patients with heterozygous genotype showed an increased hazard ratio (p = 0.02) for A23G polymorphism. G709A was associated with a reduced hazard ratio marking a better survival among mutant females (HR 0.17; p = 0.05; MST = 18.63 months). It can be concluded that A23G polymorphism might contribute to increased lung cancer risk in North Indian population emphasizing on poor survival among females. G709A polymorphism might result in protective effect in lung cancer subjects. The present study had a low sample size but it could act as reference for the large sample studies in future.

Profile of Patients with Active Tuberculosis Admitted to a Respiratory Intensive Care Unit in a Tertiary Care Center of North India.

BACKGROUND: There is a paucity of literature regarding outcome of critically ill patients with tuberculosis (TB) from India. Herein, we describe our experience of patients with active TB admitted to a Respiratory Intensive Care Unit (RICU) of a tertiary care hospital. METHODS: This was a retrospective analysis of all the patients admitted with active TB. The baseline clinical, demographic, ICU parameters and mortality were recorded. A multivariate logistic regression analysis was performed to identify factors predicting mortality. RESULTS: A total 3630 patients were admitted to the ICU during the study period; of these, 63 (1.7%) patients (mean [standard deviation (SD)] age 37.3 [19] years, 55.6% females) were admitted with active TB. Fifty-seven patients were mechanically ventilated (56, invasive and 1, noninvasive) for a mean (SD) duration of 7.5 (9.1) days. Respiratory failure was the most common indication for mechanical ventilation. TB-related acute respiratory distress syndrome was seen in 18 (28.6%) patients. There were 28 deaths (44.4%) during the study period. On a multivariate logistic regression analysis, a high baseline Acute Physiology and Chronic Health Evaluation II (APACHE II) score (odds ratio [OR] [95 confidence interval (CI)], 1.12 [1.02-1.23]) and delta Sequential Organ Failure Assessment (SOFA) (OR [95 CI], 1.39 [1.00-1.94]) were the independent predictors of mortality. CONCLUSION: TB was an uncommon cause of ICU admission even in a high TB burden country. Critically ill patients with TB had high mortality. A higher APACHE II score and delta SOFA were independent predictors of ICU mortality.

Acute Respiratory Distress Syndrome Due To Tuberculosis in a Respiratory ICU Over a 16-Year Period.

OBJECTIVE: Whether tuberculosis-related acute respiratory distress syndrome is associated with worse outcomes when compared with acute respiratory distress syndrome secondary to other causes remains unknown. Herein, we compare the outcomes between the two groups. DESIGN: Retrospective analysis of all subjects admitted with acute respiratory distress syndrome over the last 16 years. SETTING: Respiratory ICU of a tertiary care hospital in North India. SUBJECTS: Consecutive subjects with acute respiratory distress syndrome. INTERVENTION: Subjects were categorized as tuberculosis-related acute respiratory distress syndrome and acute respiratory distress syndrome-others and were managed with mechanical ventilation using the low tidal volume strategy as per the Acute Respiratory Distress Syndrom Network protocol. MEASUREMENTS AND MAIN RESULTS: The baseline clinical and demographic characteristics, lung mechanics, and mortality were compared between the two groups. Factors predicting ICU survival were analyzed using multivariate logistic regression analysis. During the study period, 469 patients (18 tuberculosis-related acute respiratory distress syndrome and 451 acute respiratory distress syndrome-others) with acute respiratory distress syndrome were admitted. The mean (SD) age of the study population (52.9% women) was 33.6 years (14.8 yr). The baseline parameters and the lung mechanics were similar between the two groups. There were 132 deaths (28.1%) with no difference between the two groups (tuberculosis-related acute respiratory distress syndrome vs acute respiratory distress syndrome-others; 27.7% vs 28.2%; p = 0.71). There was also no significant difference in the ventilator-free days, ICU, and the hospital length of stay. On multivariate logistic regression analysis, the factors predicting survival were the admission Acute Physiology and Chronic Health Evaluation II score and baseline driving pressure after adjusting for PaO2:FIO2 ratio, gender, and the etiology of acute respiratory distress syndrome. CONCLUSIONS: Tuberculosis is an uncommon cause of acute respiratory distress syndrome even in high tuberculosis prevalence countries. Acute respiratory distress syndrome due to tuberculosis behaves like acute respiratory distress syndrome due to other causes and does not affect the ICU survival.

Association of polymorphisms in Dickopff (DKK) gene towards modulating risk for lung cancer in north Indians.

AIM: To investigate the association between the genetic variants of DKK4 (rs2073664), DKK3 (rs2291599, rs3206824 and rs7391689) and DKK2 (rs447372, rs419558 and rs17037102) and lung cancer predisposition in north Indians. MATERIALS & METHODS: A total of 600 subjects were genotyped using PCR restriction fragment length polymorphism technique. Association analysis was carried out using logistic regression approach. RESULTS: DKK3 rs7396187 showed a protective effect (p = 0.01). Subjects with heterozygous genotype of DKK2 rs17037102 and rs419558 showed an increased risk. The variant genotype of the genotypic combination, DKK3 rs3206824 and DKK2 rs419558 showed a twofold increased risk (p = 0.008). Lung cancer risk increased four-times in subjects with variant genotype of all the three DKK2 variants. CONCLUSION: DKK2 is certainly playing a crucial role in modulating cancer susceptibility.

A Randomized Trial of Antimicrobial Prophylaxis in Patients Undergoing Medical Thoracoscopy (APT).

BACKGROUND: There is no data on the role of prophylactic antibiotics in patients undergoing medical thoracoscopy. OBJECTIVE: In this study, we evaluated the efficacy and safety of a single dose of intravenous cefazolin in subjects undergoing medical thoracoscopy. METHODS: Subjects undergoing medical thoracoscopy were randomized 1:1 to receive either intravenous cefazolin 2 g (antibiotic group) or intravenous saline (control group). The primary outcome was the incidence of infections (surgical site infections and empyema) in the study groups, while the secondary outcomes were complications related to intravenous antibiotics. RESULTS: Of the 121 subjects screened, 100 (mean age ± SD: 52.2 ± 15.2 years; 38 [38%] women) were randomized to the study groups. The incidence of postprocedural infections was not different between the antibiotic and the control group (4 [8%] vs. 6 [12%], p = 0.28). Surgical site infection occurred in 1 subject (2%) in the antibiotic group and 3 subjects (6%) in the saline group (p = 0.62); empyema occurred in 3 subjects (6%) in each group (p = 1.00). There was no association between age, comorbid illness (diabetes mellitus or chronic kidney disease), study group allocation, type of thoracoscope used, duration of procedure, histological diagnosis (benign or malignant), and the occurrence of infections in the postprocedural period. CONCLUSION: The use of a single dose of cefazolin prior to medical thoracoscopy was not associated with a reduction in the occurrence of postprocedural infection.

Assessing the likelihood of obstructive sleep apnea: a comparison of nine screening questionnaires.

PURPOSE: Several questionnaires are available for the screening of obstructive sleep apnea (OSA). Herein, we compare the performance characteristics of nine available questionnaires for assessing the likelihood of OSA. METHODS: Consecutive subjects who underwent polysomnography at the sleep laboratory of the unit were included. Subjects with obstructive events and apnea hypopnea index (AHI) ≥5 were considered to have OSA. The likelihood ratios (LRs) and other performance characteristics were calculated for the following nine questionnaires: Berlin, modified Berlin, STOP, STOP-Bang and OSA50 questionnaires, sleep apnea clinical score (SACS), Epworth sleepiness scale (ESS), American Society of Anesthesiologists (ASA) checklist, and the elbow sign questionnaire. RESULTS: Two-hundred and ten subjects (mean age, 46.5 years; mean body mass index [BMI], 31.9 kg/m2; 27.1% women) were included. OSA was diagnosed in 78.1% of patients; 49.5% had severe OSA (AHI ≥30). The SACS questionnaire had the highest positive LR (LR+, 5.6) and positive predictive value (95.2%). The modified Berlin questionnaire had the best negative LR (LR-, 0.2) and the highest negative predictive value (57.1%). The STOP-Bang questionnaire also had an LR- of 0.2 if BMI threshold of 25 kg/m2 (like that in the modified Berlin questionnaire) was used. Among individual items of various sleep questionnaires, the highest LR+ was obtained for neck circumference >43 cm (LR+, 4.9), while the best LR- was obtained for snoring and BMI >25 kg/m2 (LR-, 0.2). CONCLUSIONS: The SACS and the STOP-Bang questionnaires (BMI threshold of 25 kg/m2) were found to provide the best positive and negative LRs, respectively, for the prediction of OSA. We believe that information from these questionnaires may help in prioritizing patients for sleep studies in high-volume centers.