Background: On the basis of recent clinical trial data for the treatment of drug-susceptible and drug-resistant tuberculosis (TB), the American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America have updated clinical practice guidelines for TB treatment in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. Methods: A Joint Panel representing multiple interdisciplinary perspectives convened with American Thoracic Society methodologists to review evidence and make recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) and GRADE-ADOLOPMENT (adoption, adaptation, and, as needed, de novo development of recommendations) methodology. Results: New drug-susceptible TB recommendations include the use of a novel 4-month regimen for people with pulmonary TB and a shortened 4-month regimen for children with nonsevere TB. Drug-resistant TB recommendation updates include the use of novel regimens containing bedaquiline, pretomanid, and linezolid with or without moxifloxacin. Conclusions: All-oral, shorter treatment regimens for TB are now recommended for use in eligible individuals

OBJECTIVE:We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS:We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS:Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION:This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

Background The prevalence of eosinophilic asthma in Lebanon, one of the most severe phenotypes among severe asthma, is not known. This study aimed at determining the prevalence of the eosinophilic phenotype defined as an eosinophil count ≥ 300 cells/mm 3 among severe asthma patients in Lebanon. Methods The Lebanese Chapter of the PREPARE study was a national, multicenter, cross-sectional observational study. Patients aged ≥ 12 years with severe asthma were identified and prospectively enrolled during clinic visits and completed the Global Initiative for Asthma (GINA) assessment of asthma control questionnaire. Patients’ health characteristics were collected from medical records and blood samples were obtained for measurement of serum IgE levels and blood eosinophils count. Results Overall, 101 patients (with mean age of 46.3 ± 17.0 years and 73.27% females) with severe asthma were included and, among them, 37% had eosinophilic phenotype, 67.3% had atopic phenotype with IgE > 100 IU/mL and 25.7% patients had overlapping atopic and eosinophilic phenotypes. Close to 80% had late-onset asthma, beyond 12 years of age, and around 85% had at least one severe exacerbation in the 12 months prior to study enrolment. The majority of participants [64.4%] had uncontrolled asthma, 24.7% had partially controlled symptoms and 10.9% had controlled symptoms. 19.8% of participants were on chronic oral corticosteroids, 78.2% had short course treatment of corticosteroids and all were prescribed a combination of inhaled corticosteroids and long-acting beta-agonist. Conclusions The majority of patients with severe asthma were uncontrolled of which 37% present with an eosinophilic phenotype, which should be taken into consideration for better management of these patients in view of the novel phenotype-specific therapeutic options.

S1. Lung tumor development in NNK-exposed Gprc5a-/- mice. S2. Evolutionarily conserved patterns of tobacco-carcinogen mediated gene expression in murine and human airway epithelia. S3. Early and persistent changes in mouse airway gene expression in vivo following tobacco carcinogen exposure and during lung oncogenesis. S4. Gene profiles downregulated in the mouse normal-appearing airway field of injury are overall suppressed in lung tumors relative to adjacent normal lung.

INTRODUCTION: Waterpipe smoking is increasing in popularity, yet the evidence implicating waterpipe smoking in lung disease is limited. We hypothesized that impulse oscillometry (IOS) would detect airway abnormalities in waterpipe smokers (WPS). METHODS: We studied 210 participants, 40 years or older, from the community, of whom 92 were exclusive WPS and 118 were never-smokers. Waterpipe smoking history was assessed using a validated questionnaire. All participants underwent spirometry, and IOS and absolute and percentage predicted results (for age, sex, height, and weight) were compared between WPS and nonsmokers. The association of IOS parameters with waterpipe smoking duration and extent (waterpipe smoked/day * smoking duration) was evaluated using linear regression. RESULTS: WPS smoked on average 1.8 ± 1.2 waterpipes/day, over an average duration of 23.3 ± 39.8 years. WPS and nonsmokers were largely asymptomatic and had similar age, body mass index, sex distribution, and spirometric values. Nevertheless, WPS had higher IOS measured resistance at 5Hz compared to nonsmokers, (0.53 ± 0.2 vs. 0.48 ± 0.2 kPa/L/s, P = 0.03) and higher percentage-predicted resistance (124.5 ± 36.3 vs. 115.7% ± 35.6%, P = 0.04). Waterpipe smoking duration was also associated with resistance (β = 0.04 kPa/L/s/year, P = 0.01) and with percentage-predicted resistance (β = 0.05/year, P = 0.02). Waterpipe smoking extent was associated with resistance (β = 0.009 kPa/L/s/waterpipe-year, P = 0.04), while the association with percentage-predicted resistance was near significance (β = 0.009/waterpipe-year, P = 0.07). CONCLUSIONS: Waterpipe smoking is associated with increased airway resistance assessed by IOS but not by spirometry in largely asymptomatic individuals from the community.

Background Waterpipe smoking is increasing worldwide with no proven interventions for cessation. We compared abstinence rates with 12-week varenicline therapy versus placebo among habitual waterpipe smokers willing to quit. Methods This double-blind placebo-controlled single-center trial, randomized waterpipe smokers from Lebanon who did not smoke other tobacco products to receive varenicline or placebo for 12 weeks. All participants also received three structured 30-minute individual behavioral intervention sessions. The primary outcome was repeated point prevalence abstinence assessed by self-report and verified by exhaled carbon monoxide three times during 12 weeks and analyzed with the intention to treat. End of treatment urine cotinine, weight, blood pressure, anxiety, depression, withdrawal, and adverse symptoms were also assessed. Results In total, 152 waterpipe smokers (mean age 38 years [SD = 13], 39% females) willing to quit, who smoked waterpipe exclusively (average 2.3 per day [SD = 1.6] for 16.8 years [SD = 10.8]) were randomized. Seventy-nine participants (52%) with any missing abstinence assessment were considered to have relapsed. Repeat point prevalence abstinence rate was numerically higher among the varenicline group compared to placebo, but the difference did not reach statistical significance when assessed by self-report (16.9 vs. 13.6%, respectively, p = .6) and when further verified by exhaled carbon monoxide (14.1% vs. 9.9%, respectively, p = .4). Abstinence rates were similar in both groups when further verified by urine cotinine at end of treatment. No serious adverse events were reported, adverse symptoms and other outcomes were similar in the varenicline and placebo arms. Conclusions Varenicline for 12 weeks was not more effective than placebo to achieve abstinence among daily waterpipe smokers. Implications Varenicline in combination with a behavioral intervention did not significantly enhance the quit rate among exclusive waterpipe smokers compared to behavioral intervention plus placebo. We experienced difficulty enrolling exclusive waterpipe smokers willing to quit and observed high dropout rates among participants demonstrating the difficulties of waterpipe smoking cessation.

Supplementary Methods and Supplementary Figure Legends

BACKGROUND: Tobacco use via water pipe (commonly referred to as water-pipe smoking [WPS]) is popular among young adults globally and exposes those who smoke to toxicants. RESEARCH QUESTION: Is WPS associated with impaired measures of arterial function and does WPS acutely impair these measures in young adults? STUDY DESIGN AND METHODS: We assessed heart rate (HR), brachial and aortic BP, HRadjusted augmentation index (AI), and carotid-femoral pulse wave velocity (CFPWV) in 62 individuals who use water pipes and 34 individuals who have never used a water pipe recruited from the community (mean age, 22.5 +/- 3.0 years; 48% female). Measurements were obtained before and after an outdoor session of WPS among participants who use water pipes and among the control group of participants who have never used a water pipe. Measurements were compared after vs before exposure and between those who use and those who do not use water pipes, adjusting for possible confounders using linear regression. RESULTS: Participants who use water pipes and control participants had similar demographic characteristics. BP and HR increased acutely after WPS (brachial systolic BP by 4.13 mm Hg [95% CI, 1.91-6.36 mm Hg]; aortic systolic BP by 2.31 mm Hg [95% CI, 0.28-4.33 mm Hg]; brachial diastolic BP by 3.69 mm Hg [95% CI, 1.62-5.77 mm Hg]; aortic diastolic BP by 3.03 mm Hg [95% CI, 0.74-5.33 mm Hg]; and HR by 7.75 beats/min [95% CI, 5.46-10.04 beats/min]), but not in the control group. AI was significantly higher in participants who use water pipes compared with those who do not (9.02% vs 3.06%; P = .03), including after adjusting for BMI and family history of cardiovascular disease (b = 6.12; 95% CI, 0.55-11.69; P = .03) and when assessing habitual tobacco use via water-pipe extent (water pipes used/ day x water-pipe use duration) in water-pipe-years (b = 2.51/water-pipe-year; 95% CI, 0.104.92/water-pipe-year; P = .04). However, CFPWV was similar in those who use water pipes and those who do not, and AI and CFPWV did not change acutely after WPS. INTERPRETATION: In apparently healthy young individuals from the community, habitual WPS was associated with increased AI, a predictor of cardiovascular risk, and one WPS session acutely increased HR and brachial and aortic BP. CHEST 2023; 164(6):1481-1491

Supplementary Tables Table S1. Early efffcts of NNK exposure on the mouse airway transcriptome. Table S2. Evolutionarily conserved decreased gene expression in the airway following NNK exposure. Table S3. Genes differentially regulated in the mouse airway at the indicated timepoints post NNK exposure. Table S4. Mouse genes downregulated as early as T2 vs T0 and enriched in airways of human smokers with lung cancer relative to cancer-free smokers. Table S5. Pathways analysis of Mouse genes enriched in airways of human smokers with lung cancer and modulated during in vivo lung oncogenesis

Supplementary Table from Chronic Exposure to Waterpipe Smoke Elicits Immunomodulatory and Carcinogenic Effects in the Lung

Rationale: The benefit from applying suction during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is unclear. Background: The purpose of this study was to evaluate the impact of applying suction during EBUS-TBNA of lymph nodes (LN) on the diagnostic yield and specimen quality of EBUS-TBNA smears and cellblocks. Methods: We conducted a randomized blinded cross-over trial comparing the diagnostic yield and quality of EBUS-TBNA samples obtained with suction (S+) and without suction (S−) from suspected malignant mediastinal LN. Each LN was aspirated 4 times in a randomly assigned alternating order: S+/S−/S+/S− or S−/S+/S−/S+, resulting in 2 matched S+/S− smears pairs and 1 matched S+/S− cellblocks pairs. Specimen were assessed by a blinded cytopathologist. The primary outcome was the diagnostic yield of EBUS-TBNA smears and cellblocks. Secondary analyses accounted for LN size (≤2 vs. >2 cm) and station (mediastinal vs. hilar). Results: Of 234 EBUS-TBNA smears and 114 cellblocks were obtained from 59 LN. The concordance of S+ and S− cellblocks diagnostic yield was low (43.8%; 95% confidence interval: 30.7-57.6) with a significantly higher diagnostic yield among S+ compared with S− cellblocks (56.1% vs. 10.5%, respectively, P <0.001), regardless of LN station and size. However, S+ and S− smears were moderately concordant (66.7%; 95% confidence interval: 57.4-75.1) with no overall difference in their respective diagnostic yield. Numerically higher diagnostic yield among S+ smears in LN≤2 cm or hilar LN was not statistically significant. Results were similar for specimen adequacy, sensitivity and diagnosis of malignancy. Conclusion: Applying suction during EBUS-TBNA of suspected malignant LN enhanced the diagnostic yield of cellblocks regardless of mediastinal LN station or size, but not of smears.

Background Type 2 Diabetes (T2D) remains a world epidemic. Obtaining accurate estimates of its incidence and their predictors will aid in targeting preventive measures, allocating resources, and strategizing its management. The Middle East North Africa region has high T2D prevalence and rates of rise. Few incidence studies exist for the region, and none from Lebanon. The current study objective was to determine diabetes incidence and diabetes predictors in a community-based Lebanese sample. A secondary objective was to describe the metabolic control over time in adults with preexisting diabetes. Methods This is a five-year (2014–2019) follow-up study on a random sample of 501 residents of the Greater Beirut area. Out of 478 people eligible to participate in the follow-up study, 198 returned (response rate 39.5%). Assessment included medical history, anthropometric measures, food frequency, sleep, and lifestyle questionnaires. Laboratory data included glycemic indices (fasting glucose and HbA1C) and other biological markers. The diagnosis of probable diabetes (PD) was based on one abnormal test for either fasting glucose ≥ 126 mg/dL or HbA1C ≥ 6.5% or having history of diabetes. Results The incidence of diabetes was 17.2 (95% CI 9.6–28.7) per 1000 person-years. Cardiometabolic risk factors independently associated with diabetes were: older age, higher BMI, family history of diabetes, metabolic syndrome, higher CRP and triglyceride level; whereas an independent predictor of diabetes was previous BMI. In addition, the 42 participants with preexisting diabetes had worsening of their metabolic profile over a five-year period. Conclusions The incidence of diabetes was high as compared to some reported world rates, and in line with the high prevalence in the MENA region. The risk was highest in those with positive family history and the presence of the metabolic syndrome or its components. Preventive measures should particularly target participants with that specific risk profile. This becomes particularly important when observing that metabolic control gets worse over time in individuals with diabetes.

Introduction: Programmed death ligand-1 expression has been shown to be a good predictor of response to cancer therapy with checkpoint inhibitors. Its expression varies among different tumor types and among non-small cell lung cancer patients with different clinical and demographic characteristics. The prevalence and determinants of programmed death ligand-1 expression have been previously reported from various regions of the world, but data from Lebanon are lacking. This study examines the prevalence and the clinical, demographic and pathological predictors of programmed death ligand-1 expression in patients diagnosed with non-small cell lung cancer in Lebanon. Methods: Medical records of 180 patients diagnosed with primary non-small cell lung cancer at our institution and tested for programmed death ligand-1 expression were reviewed. Clinical, demographic and pathological information were collected and correlated with programmed death ligand-1 expression using the chi-square test and logistic regression. Results: One hundred eleven of the 180 non-small cell lung cancer tumor samples tested positive for programmed death ligand-1 expression (61.7%). 27.2% of those tumor samples expressed programmed death ligand-1 in 1%–49% of tumor cells, while 34.4% of tumor samples expressed programmed death ligand-1 in 50% or more of their cells. Squamous histology and advanced stage were significant predictors of programmed death ligand-1 expression (odds ratio = 2.79, 95% confidence interval [1.13–6.90], p = 0.012 and odds ratio = 2.48, 95% confidence interval [1.23–4.99], p = 0.044, respectively). Conclusion: Similar to reports from other populations, our results suggest that programmed death ligand-1 expression in non-small cell lung cancer is highly prevalent in the Lebanese population, especially in patients with advanced stage at diagnosis or squamous cell carcinoma histology. Because of the small sample size, while more that 60% of the patients are Lebanese, the results of this article cannot be extrapolated to the Middle Eastern and the Levantine population.

Abstract Purpose The evidence linking waterpipe smoking to cardiovascular disease is limited. We evaluated the association of waterpipe smoking (WPS) with arterial stiffness and wave reflection measured by augmentation pressure (AP), augmentation index (AIx), and carotid-femoral pulse wave velocity (CFPWV), which are validated predictors of cardiovascular disease. Materials and methods Community-based, cross-sectional study including 205 exclusive waterpipe smokers and 199 matched never-smokers aged 35 years or older (mean age 51.7 ± 8.9 years, 36% females). Smoking and its extent were assessed using a validated questionnaire and urine cotinine levels. CFPWV, AP, AIx (AP/aortic pulse pressure) and heart rate adjusted AIx (AIx@75) were determined using tonometry and compared between smokers and non-smokers, and the association of WPS with tonometry measures was assessed using linear regression adjusting for possible confounders. Results Waterpipe smokers and non-smokers had similar mean age and sex distribution. Compared to non-smokers, waterpipe smokers had significantly higher adjusted AP (10.5 ± 3.9 vs. 9.4 ± 3.9 mmHg respectively; p = 0.01), AIx (28.1 ± 8.4 vs. 25.7 ± 8.5% respectively; p = 0.01) and AIx@75 (24.2 ± 8.7 vs. 21.8 ± 8.9% respectively; p = 0.01). AIx was significantly associated with WPS extent, measured by a number of waterpipe smoked/day (β = 1.04/waterpipe, 95%CI:[0.50–1.58]), duration of waterpipe smoking (β = 0.77/10-years, 95%CI:[0.16–1.38]), their products in waterpipe-years (β = 0.30/10-waterpipe-year, 95%CI:[0.12–0.47]) and plasma cotinine (β = 0.56/100 ng/ml, 95%CI:[0.14–0.98]), adjusting for possible confounders, and so were AP and AIx@75. CFPWV however, was not associated with waterpipe smoking. Conclusion In a community-based sample, exclusive WPS and its extent were associated with a dose-dependent increase in AIx and AP, accounting for other risk factors, suggesting that waterpipe smokers are at increased risk of cardiovascular disease.

Rationale: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) with a diagnosis based on clinical, radiological, and pathological findings. The evidence supporting transbronchial forceps lung biopsy (TBBx) and transbronchial lung cryobiopsy (TBLC) as sampling techniques to diagnose HP in patients with newly detected ILD has not been reviewed systematically.Objectives: A systematic review was performed to assess the diagnostic yield and complication rates of TBBx or TBLC in patients with newly detected ILD whose differential diagnosis includes HP and to inform the development of the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guidelines on the diagnosis of HP.Methods: Medline, Excerpta Medica Database, and the Cochrane Library were searched through October 2019. Studies that enrolled patients with ILD and reported the diagnostic yield of TBBx or TBLC were selected for inclusion. Data related to diagnostic yield and safety outcomes were extracted and then pooled across studies via meta-analysis. The quality of the evidence was appraised using the grading of recommendations, assessment, development, and evaluation (GRADE) approach.Results: The histopathologic diagnostic yields (number of procedures that yielded a histopathologic diagnosis divided by the total number of procedures performed) of TBBx and TBLC were 37% (95% confidence interval [CI], 32-42%) and 82% (95% CI, 78-86%), respectively, among patients with ILD. Among those diagnosed by TBBx, the proportion with HP could not be determined. However, among those diagnosed by TBLC, 13.4% had HP. TBBx was complicated by moderate to severe bleeding, severe bleeding, and pneumothorax in 4% (95% CI, 0-8%), 0% (95% CI, 0-1%), and 7% (95% CI, 2-13%) of patients, respectively. TBLC was complicated by any bleeding, severe bleeding, and pneumothorax in 11% (95% CI, 7-15%), 0% (95% CI, 0-1%), and 11% (95% CI, 9-14%) of patients, respectively. The quality of the evidence was very low because of the uncontrolled study designs, lack of consecutive enrollment, and inconsistent results.Conclusions: Very low-quality evidence indicated that TBLC had a higher diagnostic yield than TBBx among patients with ILD, although complications were similar.

Rationale: Hypersensitivity pneumonitis (HP) results from exposure to a variety of stimuli, which are challenging to identify. Questionnaires and serum immunoglobulin G (IgG) testing are methods to identify potentially causative exposures. Objectives: To perform a systematic review to determine the usefulness of questionnaires and serum IgG testing in identifying exposures that may have caused HP. Methods: This systematic review informed an international, multidisciplinary panel that developed a clinical practice guideline on the diagnosis of HP for the American Thoracic Society, Japanese Respiratory Society, and Asociacion Latinoamericana del Torax. MEDLINE, the Cochrane Library, and EMBASE were searched from January 1946 to October 2019 for studies that used a questionnaire or serum IgG testing to identify exposures that may have caused HP. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to appraise the quality of the evidence. Results: Searches identified 1,141 and 926 potentially relevant articles for questionnaires and serum IgG testing, respectively. The full texts of 32 and 49 articles, respectively, were reviewed. Two observational studies for questionnaires and 15 accuracy studies for serum IgG testing were selected. Questionnaires were better at detecting potentially relevant exposures than clinical history (100% vs. 26%; risk ratio [RR], 3.80; 95% confidence interval [95% CI], 1.79-8.06) and serum IgG testing (100% vs. 63%; RR, 1.58; 95% CI, 1.12-2.23) but did not differ from serum IgG testing plus bronchial challenge testing (59% vs. 65%; RR, 0.90; 95% CI, 0.65-1.24). Longer, detailed questionnaires were more likely to lead to identification of potential exposures. Only 70% of potential exposures identified by questionnaires were subsequently confirmed by environmental testing. Serum IgG testing distinguished HP from healthy exposed and unexposed control subjects with high sensitivity (90% and 92%, respectively) and high specificity (91% and 100%, respectively) but did not distinguish HP as effectively from interstitial lung diseases (ILDs; sensitivity of 83% and specificity of 68%). Conclusions: Using a questionnaire may help clinicians identify potentially relevant exposures when evaluating a patient with newly identified ILD for HP. Serum IgG testing may also lead to identification of potentially relevant exposures, but its usefulness for distinguishing HP from other types of ILD is poor.

Background Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. Methods An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. Results The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. Conclusions The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities.

This study tried at identifying lifestyle patterns in a sample of Lebanese adults and investigating their association with metabolically healthy overweight and obesity (MHOv/O). This study used data from a community-based survey of Lebanese adults living in Greater Beirut (n = 305). Dietary intake was assessed using an 80-item food frequency questionnaire. MHOv/O was defined as having one or none of the following metabolic abnormalities: triglycerides ≥ 150 mg/dL; systolic blood pressure ≥ 130 mmHg; diastolic blood pressure ≥ 85 mmHg; fasting blood glucose ≥ 100 mg/dL; HDL-cholesterol < 40 mg/dL for men and < 50 mg/dL for women. 201 subjects were overweight/obese and 98 had MHOv/O. Factor analysis was implemented to derive lifestyle patterns. Two lifestyle patterns were identified: the unhealthy lifestyle pattern, which included foods such as fast food and soft drinks and was characterized by alcohol consumption and cigarette smoking. Eating at home loaded negatively on this pattern. The healthy lifestyle pattern was characterized by positive loadings of food groups such as milk and dairy products, fruits, vegetables and legumes. Sleep difficulties loaded negatively on this pattern, while vigorous and moderate physical activity loaded positively. Multiple logistic regression analyses showed that subjects belonging to the 3rd tertile of the healthy pattern scores had higher odds of MHOv/O as compared to those in the 1st tertile (OR 2.33, CI 1.04–4.81). Findings of this study provided evidence on the combined effect of lifestyle patterns in relation to cardiometabolic abnormalities and highlighted the importance of focusing on ‘holistic’ lifestyle pattern modifications in designing and implementing prevention interventions in overweight and obese subjects.

BACKGROUND: Water-pipe smoking is increasing in popularity, driven partly by a perception of reduced harm compared with cigarette smoking. This study evaluates the association of water-pipe smoking with coronary artery calcium (CAC), a marker of coronary heart disease (CHD) risk, in a community-based sample. METHODS: A total of 175 exclusive water-pipe smokers and 170 nonsmokers, >= 35 years of age, were recruited from the community in Lebanon and Qatar. Water-pipe smoking was assessed using a validated questionnaire. CAC score was assessed using multidetector CT scan. The association of water-pipe smoking with the presence and extent of CAC was evaluated using regression analyses adjusted for CHD risk factors. RESULTS: CAC was present in 41% of water-pipe smokers vs 28% of nonsmokers (P = .01), with an average CAC score +/- SD of 90.6 +/- 400.3 Agatston units (AUs) in water-pipe smokers and 52.4 +/- 218.6 AUs in nonsmokers. In adjusted analyses, water-pipe smokers had significantly higher adjusted odds of having CAC (OR = 2.20; 95% CI, 1.20-4.01; P = .01) and being in the high CHD risk category defined by CAC > 300 AUs (OR = 3.41; 95% CI, 1.08-10.77; P = .04) or CAC > 75% of age, sex, and race-predicted (OR = 3.11; 95% CI, 1.55-6.24; P = .001) than nonsmokers. CAC extent was significantly associated with water-pipe smoking extent measured by smoking duration (beta = 0.17/year; 95% CI, 0.05-0.29; P = .004) or the product of smoking duration and the number of water pipes smoked daily (beta = 0.04/water-pipe-year; 95% CI, 0.003-0.07; P = .03). CONCLUSION: Exclusive water-pipe smoking was associated with the presence and extent of CAC, with twice the risk of having CAC and three times the risk of being in the high CHD risk category while accounting for other risk factors.

(1) The TBX2 subfamily of transcription factors (TBXs 2, 3, 4 and 5) are markedly down-regulated in human non-small cell lung cancer (NSCLC) and exert tumor suppressor effects in lung malignancy. Yet, mechanisms underlying suppressed expression of the TBX2 subfamily in NSCLC are elusive. Here, we interrogated probable epigenetic mechanisms in suppressed expression of the TBX2 subfamily in human NSCLC. (2) TBX2 subfamily gene expression and methylation levels in NSCLC and normal lung tissues were surveyed using publicly available RNA-sequence and genome-wide methylation datasets. Methylation β-values of the four genes were statistically compared between NSCLCs and normal lung tissues, correlated with gene expression levels, and interrogated with clinicopathological variables. Expression and methylation levels of TBXs were quantified in NSCLC cells using real-time PCR and methylation-specific PCR assays, respectively. Effects of the DNA methyltransferase inhibitor 5-azacytidine (Aza) on TBX2 subfamily expression were assessed in NSCLC cells. Impact of TBX2 subfamily expression on Aza-treated cells was evaluated by RNA interference. (3) All four TBXs were significantly hypermethylated in NSCLCs relative to normal lung tissues (p < 0.05). Methylation β-values of the genes, with exception of TBX2, were significantly inversely correlated with corresponding mRNA expression levels (p < 0.05). We found no statistically significant differences in hypermethylation levels of the TBX2 subfamily by clinicopathological features including stage and tobacco history. Expression levels of the TBX genes were overall suppressed in NSCLC cells relative to normal alveolar cells. Members of the subfamily were significantly hypermethylated in all tested NSCLC cell lines relative to normal alveolar cells. Treatment with Aza induced the expression of the TBX2 subfamily concomitant with NSCLC cell growth inhibition. Further, simultaneous knockdown of the four TBX genes markedly reduced anti-growth effects of Aza in NSCLC cells. (4) Our study sheds light on new epigenetic profiles in the molecular pathogenesis of human NSCLC.