Central and Peripheral Hemodynamics in Young Adults Who Use Water Pipes and the Acute Effects of Water-Pipe Use.

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, HR-adjusted 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 (ß = 6.12; 95% CI, 0.55-11.69; P = .03) and when assessing habitual tobacco use via water-pipe extent (water pipes used/day × water-pipe use duration) in water-pipe-years (ß = 2.51/water-pipe-year; 95% CI, 0.10-4.92/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.

Increased airway resistance among exclusive waterpipe smokers detected using impulse oscillometry.

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 (ß = 0.04 kPa/L/s/year, P = 0.01) and with percentage-predicted resistance (ß = 0.05/year, P = 0.02). Waterpipe smoking extent was associated with resistance (ß = 0.009 kPa/L/s/waterpipe-year, P = 0.04), while the association with percentage-predicted resistance was near significance (ß = 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.

Varenicline Treatment for Waterpipe Smoking Cessation.

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.

Copper Deficiency and Polyneuropathy: A Case Report.

Although copper plays a pivotal role in numerous physiological processes, its deficiency is virtually indistinguishable from subacute combined degeneration due to cobalamin deficiency. Moreover, the co-occurrence of deficiencies in other micronutrients and vitamins is common, making the diagnosis even more challenging. Here, we describe a case of copper deficiency in a 50-year-old woman who presented with altered mental status and bilateral upper and lower extremity weakness, numbness, and paresthesia. She was treated for cirrhosis and hepatic encephalopathy secondary to hepatic injury. While her mental symptoms improved, her physical symptoms continued to worsen, and she was transferred for further evaluation. The neurologic examination was positive for sensory neuropathy including decreased vibration/proprioception and ataxia in arms and legs; complete blood count showed pancytopenia; but infectious workup, cerebrospinal fluid analysis, autoimmune studies, and brain/spine magnetic resonance imaging were normal. A nerve conduction study showed generalized, axonal sensorimotor polyneuropathy. Micronutrient/trace element deficiency was suspected in the setting of gastric bypass surgery, and supplementation was successfully initiated. Though uncommon, clinical copper deficiency is increasingly frequently recognized in the inpatient setting, and permanent neurological damage can occur prior to diagnosis and treatment. Physicians should have an elevated clinical suspicion of copper deficiency in cases of polyneuropathy and pancytopenia in patients with a history of bariatric surgery.

Randomized Cross-over Trial of Endobronchial Ultrasound Transbronchial Needle Aspiration With or Without Suction in Suspected Malignant Lymphadenopathy.

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.

The association of waterpipe smoking with arterial stiffness and wave reflection in a community-based sample.

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 (ß = 1.04/waterpipe, 95%CI:[0.50-1.58]), duration of waterpipe smoking (ß = 0.77/10-years, 95%CI:[0.16-1.38]), their products in waterpipe-years (ß = 0.30/10-waterpipe-year, 95%CI:[0.12-0.47]) and plasma cotinine (ß = 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.

Transbronchial Biopsy and Cryobiopsy in the Diagnosis of Hypersensitivity Pneumonitis among Patients with Interstitial Lung 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.

Updated guidance on the management of COVID-19: from an American Thoracic Society/European Respiratory Society coordinated International Task Force (29 July 2020).

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.

Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.

Background: This guideline addresses the diagnosis of hypersensitivity pneumonitis (HP). It represents a collaborative effort among the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.Methods: Systematic reviews were performed for six questions. The evidence was discussed, and then recommendations were formulated by a multidisciplinary committee of experts in the field of interstitial lung disease and HP using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.Results: The guideline committee defined HP, and clinical, radiographic, and pathological features were described. HP was classified into nonfibrotic and fibrotic phenotypes. There was limited evidence that was directly applicable to all questions. The need for a thorough history and a validated questionnaire to identify potential exposures was agreed on. Serum IgG testing against potential antigens associated with HP was suggested to identify potential exposures. For patients with nonfibrotic HP, a recommendation was made in favor of obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte cellular analysis, and suggestions for transbronchial lung biopsy and surgical lung biopsy were also made. For patients with fibrotic HP, suggestions were made in favor of obtaining BAL for lymphocyte cellular analysis, transbronchial lung cryobiopsy, and surgical lung biopsy. Diagnostic criteria were established, and a diagnostic algorithm was created by expert consensus. Knowledge gaps were identified as future research directions.Conclusions: The guideline committee developed a systematic approach to the diagnosis of HP. The approach should be reevaluated as new evidence accumulates.

Sleepless in Beirut: sleep duration and associated subjective sleep insufficiency, daytime fatigue, and sleep debt in an urban environment.

PURPOSE: Insufficient sleep is not well studied in developing countries. We assessed sleep duration among adults in Lebanon and examined its potential predictors and relationship with subjective sleep insufficiency, daytime fatigue, and weekday sleep debt. METHODS: This cross-sectional study included 501 adults (mean age 45.2 (SD15.2) years, 64% females) from the community in Beirut and Mount Lebanon. Socio-demographic, lifestyle and health characteristics, subjective sleep insufficiency, daytime fatigue, and weekday sleep debt (weekend vs. weekdays sleep duration) were compared between individuals who reported sleeping < 6:00, 6-7:59(reference), or ≥ 8:00 h/night. Symptoms and predictors of sleep duration were assessed using logistic regression. RESULTS: Thirty-nine percent of participants reported sleeping < 6 h/night while 15% reported sleeping ≥ 8:00 h/night. Age (OR = 1.16/year, 95% CI [1.02-1.33]) and female sex (OR = 1.71, 95% CI [1.14-2.58]) were significant predictors of short sleep (< 6:00 h/night) in multivariable adjusted analyses. Compared to referent (6:00-7:59 h/night) and long sleepers (≥ 8:00 h/night), short sleepers were significantly more likely to report subjective sleep insufficiency (OR = 3.00, 95% CI [2:00-4.48], and OR = 4.52, 95% CI [2.41-8.51]; respectively) and daytime fatigue (OR = 1.53, 95% CI [1.04-2.24], and OR = 1.83, 95% CI [1.06-2.04]; respectively). Compared to long weekdays sleepers, short and referent weekdays sleepers were more likely to sleep longer on weekend (OR = 2.47, 95% CI [1.18-5.15], and OR = 4.16, 95% CI [2.03-8.5]; respectively). CONCLUSIONS: Short sleep is highly prevalent in this urban cohort from a low- to medium-income country especially among women and older adults, and is associated with subjective sleep insufficiency, daytime fatigue, and weekday sleep debt. The socio-cultural determinants of sleep duration need to be studied across different populations to better evaluate the causes and implications of short sleep.

Sleepless in Beirut: Sleep Difficulties in an Urban Environment With Chronic Psychosocial Stress.

STUDY OBJECTIVES: The prevalence of sleep disorders in the Lebanese population is unknown. We assessed the prevalence of insomnia and sleep apnea risk and examined their relationship with sociodemographic, lifestyle, and health characteristics in a sample from Greater Beirut. METHODS: This cross-sectional pilot survey included 501 adults from the community (age 45.2 ± 15.2 years, 64% females). Insomnia symptoms, insomnia disorder, and sleep apnea risk were assessed using the Sleep Heart Health Study and Berlin Questionnaire. Characteristics were compared between individuals with and without insomnia symptoms, insomnia disorder, and sleep apnea. Correlates were assessed using multivariate regression. RESULTS: A total of 44.5% of participants reported insomnia symptoms > 15 nights/mo and 34.5% reported insomnia. Predictors of insomnia symptoms and disorder included female sex (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.01-2.27 and OR 1.76, 95% CI 1.13-2.75, respectively), education level below high school (OR 1.96, 95% CI 1.31-2.95 and OR 2.40, 95% CI 1.52-3.77, respectively) and medical comorbidities (OR 2.27, 95% CI 1.30-3.95 and OR 3.02, 95% CI 1.3-5.27, respectively). Although 31% of participants were at high risk for sleep apnea, only 5% received the diagnosis from a physician. Increased sleep apnea risk was associated with unemployment (OR 1.96, 95% CI 1.11-3.49), high body mass index (OR 1.17, 95% CI 1.11-1.24), snoring (OR 16.7, 95% CI 9.0-31.0), hypertension (OR 4.33, 95% CI 2.28-8.22), arthritis (OR 2.00, 95% CI 1.01-4.01), and other medical comorbidities (OR 2.65, 95% CI 1.24-5.68). CONCLUSIONS: Insomnia and sleep apnea are highly prevalent and likely underdiagnosed in this cohort from Lebanon and are associated with disadvantaged socioeconomic status and medical comorbidities. This alarming prevalence of sleep difficulties and disorders calls for future research exploring the causes including the potential effect of social, economic, and political instability, mental and psychological stress, local customs, and environmental factors.

The Association of Water-Pipe Smoking and Coronary Artery Calcium in a Community-Based Sample.

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 (ß = 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 (ß = 0.04/water-pipe-year; 95% CI, 0.003-0.07; P = .03). CONCLUSIONS: 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.

The association between sleep-disordered breathing and aortic stiffness in a community cohort.

OBJECTIVE: Sleep-disordered breathing is associated with hypertension and cardiovascular disease. Increased aortic stiffness is one possible linking mechanism. We evaluated the association between sleep-disordered breathing and aortic stiffness in a community-based sample. METHODS: Our community-based cross-sectional observational study included 381 participants from the Framingham Heart Study (55% women, mean age 58.0 S.D. = 9.4 years, 51% ethnic minorities). Polysomnographically derived apnea-hypopnea index and CT90% (cumulative % sleep time with oxyhemoglobin saturation <90%) quantified sleep-disordered breathing severity. Carotid-femoral pulse wave velocity, the gold-standard measure of aortic stiffness, was calculated using arterial applanation tonometry-derived waveforms and body surface measured transit distance. We assessed associations between sleep-disordered breathing and carotid-femoral pulse wave velocity using multivariable regression. We adjusted for age, sex, race, body mass index, diabetes, alcohol consumption, hormone replacement therapy, cholesterol/high-density lipoprotein, lipid-lowering therapy, anti-hypertensive medication, smoking, hypertension, and prevalent cardiovascular disease. RESULTS: After multivariable adjustment, carotid-femoral pulse wave velocity was associated with both apnea-hypopnea index (ß = 0.03, 95% CI: 0.002-0.07, p= 0.04) and CT90% (ß = 0.05, 95% CI: 0.005-0.1, p= 0.03). The adjusted mean carotid-femoral pulse wave velocity was 9.43 (95% CI: 9.12-9.74), 9.76 (95% CI: 9.25-10.26), and 10.15 (95% CI: 9.37-10.92) m/s, respectively, in subjects with apnea-hypopnea index <5, 5-14.9, and ≥15 events/h. CONCLUSIONS: In a community-based sample of middle aged and older men and women, sleep-disordered breathing was associated with increased carotid-femoral pulse wave velocity, a strong predictor of cardiovascular risk.

Association between Glucose Metabolism and Sleep-disordered Breathing during REM Sleep.

RATIONALE: Sleep-disordered breathing (SDB) has been associated with impaired glucose metabolism. It is possible that the association between SDB and glucose metabolism is distinct for non-REM versus REM sleep because of differences in sleep-state-dependent sympathetic activation and/or degree of hypoxemia. OBJECTIVES: To characterize the association between REM-related SDB, glucose intolerance, and insulin resistance in a community-based sample. METHODS: A cross-sectional analysis that included 3,310 participants from the Sleep Heart Health Study was undertaken (53% female; mean age, 66.1 yr). Full montage home-polysomnography and fasting glucose were available on all participants. SDB severity during REM and non-REM sleep was quantified using the apnea-hypopnea index in REM (AHIREM) and non-REM sleep (AHINREM), respectively. Fasting and 2-hour post-challenge glucose levels were assessed during a glucose tolerance test (n = 2,264). The homeostatic model assessment index for insulin resistance (HOMA-IR) was calculated (n = 1,543). Linear regression was used to assess the associations of AHIREM and AHINREM with fasting and post-prandial glucose levels and HOMA-IR. MEASUREMENTS AND MAIN RESULTS: AHIREM and AHINREM were associated with fasting glycemia, post-prandial glucose levels, and HOMA-IR in models that adjusted for age, sex, race, and site. However, with additional adjustment for body mass index, waist circumference, and sleep duration, AHIREM was only associated with HOMA-IR (ß = 0.04; 95% CI, 0.1-0.07; P = 0.01), whereas AHINREM was only associated with fasting (ß = 0.93; 95% CI, 0.14-1.72; P = 0.02) and post-prandial glucose levels (ß = 3.0; 95% CI, 0.5-5.5; P = 0.02). CONCLUSIONS: AHIREM is associated with insulin resistance but not with fasting glycemia or glucose intolerance.

Health effects associated with waterpipe smoking.

OBJECTIVE: It is widely held that waterpipe smoking (WPS) is not associated with health hazards. However, several studies have documented the uptake of several toxicants and carcinogens during WPS that is strongly associated with harmful health effects. This paper reviews the literature on the health effects of WPS. DATA SOURCES: Three databases-PubMed, MEDLINE and EMBASE-were searched until August 2014 for the acute and long-term health effects of WPS using the terms 'waterpipe' and its synonyms (hookah, shisha, goza, narghileh, arghileh and hubble-bubble) in various spellings. STUDY SELECTION: We included original clinical studies, case reports and systematic reviews and focused on clinical human studies. ∼10% of the identified studies met the selection criteria. DATA EXTRACTION: Data were abstracted by all three authors and summarised into tables. Abstracted data included study type, results and methodological limitations and were analysed jointly by all three authors. DATA SYNTHESIS: WPS acutely leads to increased heart rate, blood pressure, impaired pulmonary function and carbon monoxide intoxication. Chronic bronchitis, emphysema and coronary artery disease are serious complications of long-term use. Lung, gastric and oesophageal cancer are associated with WPS as well as periodontal disease, obstetrical complications, osteoporosis and mental health problems. CONCLUSIONS: Contrary to the widely held misconception, WPS is associated with a variety of adverse short-term and long-term health effects that should reinforce the need for stronger regulation. In addition, this review highlights the limitations of the published work, which is mostly cross-sectional or retrospective. Prospective studies should be undertaken to assess the full spectrum of health effects of WPS, particularly in view of its growing popularity and attractiveness to youth.

Vascular inflammation and sleep disordered breathing in a community-based cohort.

STUDY OBJECTIVES: Sleep disordered breathing is associated with cardiovascular disease. The pathophysiologic mechanisms remain unclear, but enhanced vascular inflammation is implicated. We sought to evaluate the association of sleep disordered breathing with biomarkers of inflammation. DESIGN: Cross-sectional, observational. SETTING: Community-based. PARTICIPANTS: There were 900 participants from the Framingham Heart Study site of the Sleep Heart Health Study (52% females, mean age 60 y, 23% ethnic minorities). INTERVENTIONS: None. MEASUREMENTS: We assessed circulating levels of nine inflammatory biomarkers in relation to polysomnographically-derived apnea-hypopnea index and hypoxemia index (% sleep time with oxyhemoglobin saturation < 90%). Multivariable models were adjusted for demographics, smoking, cardiovascular diseases, diabetes, and other potential confounders, without and with adjustment for body mass index. RESULTS: With multivariable adjustment not including body mass index, the apnea-hypopnea index was associated with C-reactive protein, inter-leukin-6, fibrinogen, intercellular adhesion molecule-1, and P-selectin levels and hypoxemia index was associated with C-reactive protein, interleukin-6, and fibrinogen levels. After adjustment for body mass index, only the association of interleukin-6 with sleep disordered breathing remained significant: the adjusted mean serum interleukin-6 level was 2.93, 3.14, 3.34, and 4.62 pg/mL, respectively, in participants with apnea-hypopnea index < 5, 5-14.9, 15-29.9, and ≥ 30 events/h (P = 0.01 for trend) and 2.97, 3.01, 3.35, and 4.85 pg/mL, respectively, in participants with hypoxemia index < 0.5, 0.5-4.9, 5-9.9, and ≥ 10% of sleep time (P = 0.02 for trend). CONCLUSIONS: In a community-based sample, sleep disordered breathing is associated with higher levels of interleukin-6, a marker of myocardial infarction risk and mortality. Adiposity may mediate the increased levels of C-reactive protein, fibrinogen, intercellular adhesion molecule-1, and P-selectin observed in sleep disordered breathing.

Association of incident cardiovascular disease with progression of sleep-disordered breathing.

BACKGROUND: Prospective data suggest that sleep-disordered breathing enhances risk for incident and recurrent cardiovascular disease (CVD). However, a reverse causal pathway whereby incident CVD causes or worsens sleep-disordered breathing has not been studied. METHODS AND RESULTS: A total of 2721 Sleep Heart Health Study participants (mean age 62, standard deviation=10 years; 57% women; 23% minority) without CVD at baseline underwent 2 polysomnograms 5 years apart. Incident CVD events, including myocardial infarction, congestive heart failure, and stroke, were ascertained and adjudicated. The relation of incident CVD to change in apnea-hypopnea index between the 2 polysomnograms was tested with general linear models, with adjustment for age, sex, race, study center, history of diabetes mellitus, change in body mass index, change in neck circumference, percent sleep time spent in supine sleep, and time between the 2 polysomnograms. Incident CVD occurred in 95 participants between the first and second polysomnograms. Compared with participants without incident CVD, those with incident CVD experienced larger increases in apnea-hypopnea index between polysomnograms. The difference in adjusted mean apnea-hypopnea index change between subjects with and without incident CVD was 2.75 events per hour (95% confidence interval, 0.26 to 5.24; P=0.032). This association persisted after subjects with central sleep apnea were excluded. Compared with participants without incident CVD, participants with incident CVD had greater increases in both mean obstructive and central apnea indices, by 1.75 events per hour (95% confidence interval, 0.10 to 1.75; P=0.04) and by 1.07 events per hour (95% confidence interval, 0.40 to 1.74; P=0.001), respectively. CONCLUSIONS: In a diverse, community-based sample of middle-aged and older adults, incident CVD was associated with worsening sleep-disordered breathing over 5 years.

Sleepiness, quality of life, and sleep maintenance in REM versus non-REM sleep-disordered breathing.

RATIONALE: The impact of REM-predominant sleep-disordered breathing (SDB) on sleepiness, quality of life (QOL), and sleep maintenance is uncertain. OBJECTIVE: To evaluate the association of SDB during REM sleep with daytime sleepiness, health-related QOL, and difficulty maintaining sleep, in comparison to their association with SDB during non-REM sleep in a community-based cohort. METHODS: Cross-sectional analysis of 5,649 Sleep Heart Health Study participants (mean age 62.5 [SD = 10.9], 52.6% women, 22.6% ethnic minorities). SDB during REM and non-REM sleep was quantified using polysomnographically derived apnea-hypopnea index in REM (AHI(REM)) and non-REM (AHI(NREM)) sleep. Sleepiness, sleep maintenance, and QOL were respectively quantified using the Epworth Sleepiness Scale (ESS), the Sleep Heart Health Study Sleep Habit Questionnaire, and the physical and mental composites scales of the Medical Outcomes Study Short Form (SF)-36. MEASUREMENTS AND MAIN RESULTS: AHI(REM) was not associated with the ESS scores or the physical and mental components scales scores of the SF-36 after adjusting for demographics, body mass index, and AHI(NREM) x AHI(REM) was not associated with frequent difficulty maintaining sleep or early awakening from sleep. AHI(NREM) was associated with the ESS score (beta = 0.25; 95% confidence interval [CI], 0.16 to 0.34) and the physical (beta = -0.12; 95% CI, -0.42 to -0.01) and mental (beta = -0.20; 95% CI, -0.20 to -0.01) components scores of the SF-36 adjusting for demographics, body mass index, and AHI(REM). CONCLUSIONS: In a community-based sample of middle-aged and older adults, REM-predominant SDB is not independently associated with daytime sleepiness, impaired health-related QOL, or self-reported sleep disruption.