Fahed Hakim

The acute effects of water-pipe smoking on the cardiorespiratory system.

OBJECTIVEnThere are limited data on the acute effects of water-pipe tobacco smoking, commonly known as water-pipe smoking (WPS), on cardiopulmonary parameters. This study evaluated the acute effects of a single 30-min session of WPS on carboxyhemoglobin (COHb) levels, pulmonary function test results, vital signs, fractional exhaled nitric oxide (Feno) levels, and exhaled breath condensate (EBC) cytokine levels in volunteers in a domestic, open-air, group smoking setting.nnnMETHODSnThis prospective study evaluated the above-noted outcome parameters before and after 30 min of WPS. The primary outcome parameter was the change in COHb levels.nnnRESULTSnForty-five volunteers (30 men, 15 women), aged 32.35 ± 15.33 years, were recruited. After one session of WPS, the COHb levels rose significantly, from 1.47% ± 0.57% (median 1.4) to 9.47% ± 5.52% (median 7.4), P < .001. Systolic and diastolic BP levels significantly increased after smoking (systolic, 119.52 ± 12.07 mm Hg vs 131.98 ± 17.8 mm Hg; diastolic, 74.84 ± 7.89 mm Hg vs 82.98 ± 12.52 mm Hg, respectively; P < .001). Heart rates increased from 80.39 ± 9.92 beats/min to 95.59 ± 17.41 beats/min, P < .001; and respiratory rates increased from 14.36 ± 1.63 breaths/min to 16.68 ± 2.24 breaths/min, P < .001. There were decreases in forced expiratory flow between 25% and 75% of FVC, peak expiratory flow rate, Feno levels, percentage of eosinophils in peripheral blood, and 8-isoprostane levels in EBC.nnnCONCLUSIONSnThis study shows that one session of WPS causes acute biologic changes that might result in marked health problems. It adds to the limited evidence that WPS is harmful and supports interventions to control the continuing global spread of WPS, especially among youth.nnnTRIAL REGISTRYnClinicalTrials.gov; No.: NCT01157832; URL: www.clinicaltrials.gov.

Vitamins a and e and pulmonary exacerbations in patients with cystic fibrosis

Background: Increased levels of oxidative stress result in pulmonary damage contributing to the development of chronic lung disease in cystic fibrosis (CF). The aim of this study was to investigate the longitudinal effect of serum vitamin A and E levels on the incidence of pulmonary exacerbations in pancreatic insufficient (PI) and pancreatic sufficient (PS) patients with CF. Materials and Methods: Patient records were retrospectively examined over a 3-year period and serum vitamin A and E levels were retrieved. Subsequently, levels of vitamin A and E were prospectively measured over a 2-year period at the onset of intravenous antibiotic therapy for acute exacerbation and at the first recovery visit. Results: Retrospectively, 597 pulmonary exacerbations were identified in 102 patients, 74 PI and 28 PS, with a mean age of 11.1 ± 6.4 years (range, 1.5–27 y). An increased number of exacerbations was directly correlated with lower vitamin A and E levels, even within the normal range. Prospectively, 62 exacerbations were analyzed (43 PI patients and 19 PS patients). At onset of exacerbation, vitamin A and E levels were reduced in the PI patients (P < 0.001; P < 0.001) and the PS patients (P < 0.005; P < 0.07). Conclusions: Reduced serum levels of vitamin A and E even in the normal range are associated with an increased rate of pulmonary exacerbations in CF. Further studies are required to confirm the necessity of supplementation of vitamins A and E to PS patients.

FRC measurements using body plethysmography in young children.

Measurement of FRC in whole body plethysmography (FRCpleth) is not performed in young children (aged 3–5 years) because it involves sitting alone in a closed box and breathing attempts against occlusion.

Reduced vital capacity after methacholine challenge in early childhood – Is it due to trapped air or loss of motivation

UNLABELLEDnIn a previous study we assessed the feasibility of measuring bronchial-reactivity (BHR) in young asthmatic children by the determination of PC(20)-FEV(1) along with clinical end-of-test criteria during a methacholine challenge test (MCT). The end-point was associated with a significant reduction in both flow and vital capacity values. The findings could be due to the childrens loss of motivation, which may preclude use of this test. Alternatively, if it reflects air trapping during airway obstruction, it might reinforce its applicability in preschool age children.nnnOBJECTIVESnTo elucidate the mechanism of low vital capacity at PC(20)-FEV(1) in preschool age children.nnnSUBJECTSnTwenty-eight children (3.3-6.9 years) with recurrent respiratory symptoms.nnnMETHODSnAn MCT was carried out using tripling doses (0.06-13.9 mg/ml) delivered by a dosimeter. Spirometry was measured at baseline and after each inhalation in duplicate sets. Whole body plethysmography was measured at baseline and at end-of-test (defined by clinical criteria) according to the recommendations for older populations.nnnRESULTSnPlethysmography was reliably performed by 20 children before and after MCT. At baseline, lung function was within the healthy range. At end-of-test (PC(20)-FEV(1)=4.02+/-3.47 mg/ml), the spirometry parameters and specific conductance values were markedly reduced in correlation with a significant increase in residual volume and resistance.nnnCONCLUSIONSnThe study shows that diminished vital capacity is due to the increase in FRC at end-of-test. Our findings support the use of PC(20)-FEV(1) during BHR in young children and suggest that lung volume measurement by a plethysmograph may be feasible in early childhood. Larger studies should be performed to establish the clinical applicability of PC20-FEV1 determination in the preschool age.

Airway reactivity in children before and after stem cell transplantation

Stem cell transplantation (SCT) is associated with pulmonary complications. We encountered several children post‐SCT with a clinical picture suggestive of airway hyper‐reactivity (AHR) and evidence of reversible airway obstruction that was not reported pre‐transplant.

Is capnometry helpful in children with bronchiolitis

BACKGROUNDnAcute bronchiolitis is the most frequent lower respiratory tract infection in infants. Only small subsets of patients develop severe disease resulting in hospitalization despite having no identifiable risk factors. There is still a debate as to the role of capnometry in assessing ventilation in children with acute respiratory distress, and bronchiolitis in particular.nnnMETHODSnThis was a prospective, single blind cohort study in which children younger than two years presenting to the emergency department (ED) with bronchiolitis were included. Our primary outcome was the correlation between the end tidal CO2 (EtCO2) and the clinical decision of hospital admission and discharge. Our secondary outcome measure was the correlation of EtCO2 upon arrival to the ED and clinical measures of bronchiolitis severity. Finally, by using multivariate models, we looked for other parameters that could contribute to the prediction of illness severity.nnnRESULTSnOne hundred and fourteen children with bronchiolitis were evaluated. Their median EtCO2 upon arrival to the ED was 34 mmHg (range 24-65 mmHg). EtCO2 values upon admission or discharge were not statistically different among patients who were hospitalized and among those who were discharged from the ED. Among admitted patients, we found no correlation between capnometry readings at admission and number of oxygen desaturation days, nor with the length of hospitalization. Wang clinical respiratory severity score was found, by using multivariate models, to predict nasogastric tube need, oxygen desaturation days, and length of hospitalization.nnnCONCLUSIONnCapnometry readings upon arrival to the ED did not predict hospital admission or hospital discharge eligibility. Among hospitalized patients, EtCO2 did not correlate with the evaluated disease severity measures. Wang score was found to be the most consistent predictor of significant outcomes.

Nationwide genetic analysis for molecularly unresolved cystic fibrosis patients in a multiethnic society: implications for preconception carrier screening

Preconception carrier screening for cystic fibrosis (CF) is usually performed using ethnically targeted panels of selected mutations. This has been recently challenged by the use of expanded, ethnically indifferent, pan‐population panels. Israel is characterized by genetically heterogeneous populations carrying a wide range of CFTR mutations. To assess the potential of expanding the current Israeli preconception screening program, we sought the subset of molecularly unresolved CF patients listed in the Israeli CF data registry comprising ~650 patients.

Intermittent inhaled tobramycin and systemic cytokines response in CF patients with Pseudomonas aeruginosa

INTRODUCTIONnCF pulmonary guidelines recommend alternate therapy (one month on, one month off) with inhaled tobramycin for chronic Pseudomonas aeruginosa colonization in cystic fibrosis (CF). Tobramycin-inhaled powder (TIP™) is increasingly replacing time-consuming nebulizer therapy. It is unclear whether laboratory parameters change during the month off period compared with the month on therapy.nnnPURPOSEnOur aim was to assess whether spirometry, lung clearance index and circulating inflammatory markers differ between on/off treatment periods.nnnMATERIALS AND METHODSnA prospective pilot study evaluating CF patients treated with TIP, on two consecutive months (on/off) therapy. The evaluations were performed at the end of a month off therapy (1-2 days before the initiation of TIP) and after 28 days of treatment with TIP (1-2 days after the end of the treatment cycle).nnnRESULTSnNineteen CF patients (10 males) with a mean age of 18.7±9.7 years and BMI (body mass index) of 19.62±3.53 kg/m2 were evaluated. After a month off treatment with TIP, spirometry parameters and lung clearance index remained unchanged. IL-6 increased significantly (p=0.022) off treatment. There was a non-significant change in the other inflammatory cytokines off therapy [hs-CRP, IL-8,TNF-α, α1-antitrypsin (α1AT) and neutrophilic elastase].nnnCONCLUSIONSnThe results of lung function parameters support the relative stability of CF patients during the month off therapy; however, the difference in serum IL-6 raises the possibility of ongoing higher degrees of inflammation during the month off therapy with TIP. The small sample size and the multiple parameters evaluated preclude firm conclusions; therefore, larger multicenter studies are needed to assess the on/off treatment strategy.

Sleep Disturbance and Cancer—Animal Models

Sleep-disordered breathing (SDB) has been linked to wide range of adverse physiologic and pathologic features, from cognitive impairments to increased risk of cancer. In this current review, we will discuss some of the emerging evidence connecting sleep disruption with cancer, by exploring different models of sleep disorders and how they appear to affect cancer. Then, we will summarize our current understanding of the underlying mechanisms, and finally, we will discuss the impact of sleep on one of the frequent and advanced cancer therapies, namely bone marrow transplantation (BMT). Experiments in animal models provide supportive findings, whereby each of the major components of SDB has begun to unravel their potential and complex effects on cancer biology, most likely via alterations in oxidative stress, angiogenesis, immune function, and sympathetic outflow. Future research is undoubtedly needed to better understand the pathophysiologic mechanisms of SDB-related effects on cancer in general, and more specifically on cancer prevention, treatment (chemotherapy, radiation, BMT), and outcomes.

Assessment of Airway Bronchodilation by Spirometry Compared to Airway Obstruction in Young Children with Asthma

A reversibility test by an increase of greater than 12% in FEV1 can support a diagnosis of asthma and alter a patients treatment plan but may not be applicable to the young ages. We retrospectively gathered spirometric data from 85/271 asthmatic children having mild obstruction (FEV1 > 80% predicted), age 2.6–6.9 years. Spirometry was performed before and 20u2009min after inhalation of 200u2009mcg Albuterol. We defined a deviation below −1.64 z scores from control as obstruction and an increased above 1.64 scores from control as a positive response to bronchodilators. Sensitivity of the index was considered significant if it captured >68% of the participants. The sensitivity of detecting airway obstruction in these children by FEV1 was 15.3% and 62.4% by FEF25–75. A positive response to Albuterol was an increase of 9.2% for FEV1 (12% for adults) and 18.5% for FEF25–75. The sensitivity for detecting a response to Albuterol in mild asthma was 64.7% by FEV1 and 91.8% by FEF25–75. Young children having normal spirometry can demonstrate airway reversibility. The response of spirometry parameters to bronchodilators may be more sensitive than obstruction detection and may help to support the diagnosis of asthma and adjust treatment plan.