José Miguel Chatkin

Diretrizes para cessação do tabagismo: 2008

These guidelines are an up-to-date and comprehensive tool to aid health professionals in treating smokers, recommending measures and strategies for managing each case based on clinical evidence. Written in a simplified and objective manner, the text is divided into two principal sections: Evaluation and Treatment. The sections both present comments on and levels of evidence represented by the references cited, as well as some proposals for the reduction of damage and for intervening in specific and still poorly explored situations, such as relapse, passive smoking, physician smoking, and tobacco use in specific environments.

Diretrizes para Cessação do Tabagismo

Universidade Federal do Rio de Janeiro (UFRJ) Hospital Universitario Clementino Fraga Filho

Exhaled nitric oxide in chronic obstructive pulmonary disease: relationship to pulmonary function

The following study was undertaken in order to determine how exhaled nitric oxide (eNO) levels in former smokers with chronic obstructive pulmonary disease (COPD) compared to eNO levels in patients with asthma and in healthy nonsmoking volunteers. The study also aimed to determine any relationship between eNO levels in COPD and: 1) conventional measures of lung function; and 2) inhaled corticosteroid (ICS) use. In former smokers with COPD, nonsmokers with asthma and volunteers, eNO levels, spirometry, lung volumes, carbon monoxide diffusion capacity of the lung (DL,CO) and resting oxygen saturation (Sa,O2) were measured. Median eNO was significantly higher among patients with COPD than among healthy volunteers (p = 0.003) but lower than among patients with asthma (p < 0.01). There was no significant difference in eNO levels between COPD patients using ICS and those not using ICS. By contrast, eNO was lower among asthma patients who used ICS (median 32 parts per billion (ppb); 25-75% range 16-54) than among asthma patients who did not (51 ppb; 32-87) (p = 0.034). Among patients with COPD, eNO was inversely correlated with forced expiratory volume in one second, DL,CO and Sa,O2, and was positively correlated with the residual lung volume/total lung capacity ratio. Among patients with asthma, no significant correlations were found. Exhaled nitric oxide is increased in patients with chronic obstructive pulmonary disease, an increase that is influenced by structural abnormalities of tobacco-induced lung damage.

Nasal nitric oxide: a comparison of measurement techniques.

Nasal nitric oxide measurement may be a surrogate marker of upper airway inflammation. There is, however, no standardized measurement technique; and this led us to examine measurement techniques for acceptability and reproducibility. In five subjects we examined the flow dependence of nasal NO. In 13 healthy volunteers, nasal NO was measured on-line by five methods: 1) Tidal nasal and oral breathing: NO sampling during exclusive nasal followed by exclusive oral tidal breathing; 2) Fixed flow exhalation: NO sampling during exclusive nasal followed by exclusive oral exhalation at 100 mL/second from total lung capacity; 3) Nasal-oral aspiration: air aspirated from the mouth via both nares at 100 mL/second with glottis closure; 4) Aspiration from one nares: air aspirated from one nares at 3.3 mL/second using nitric oxide analyzer sample line with velum closure; 5) Nasal Insufflation: NO sampled at one nares as air insufflated into the other nares at a flow of 100 mL/second with velum closure. Acceptability of all methods was assessed by subjects and technicians. Nasal NO concentration showed a significant inverse correlation with transnasal flow rate. All methods showed excellent reproducibility as assessed by the intraclass correlation coefficient except tidal breathing, which showed highly variable breath-to-breath NO levels, although mean breath values were reproducible. Mean nasal NO concentrations with methods 1, 2, 3, 4, and 5 were 32.1, 50.2, 62.8, 1381, and 60.0 ppb, respectively. Velum closure was not always achieved in methods 4 and 5, whereas methods 1 and 2 required separate nasal and oral procedures. Method 5 had reduced acceptability. NO concentrations were similar with methods that used the same airflow (2, 3, and 5). Nasal NO can be sampled in different ways with excellent reproducibility. In view of the flow dependence of nasal NO, it is vital to use a constant flow rate, and lower airway NO contribution must be excluded or subtracted. The fixed flow exhalation appears to be the preferred method as it is highly reproducible and acceptable.

Aerodynamic Influences on Nasal Nitric Oxide Output Measurements

Nitric oxide (NO) concentration in aspirated nasal air is flow-dependent. Nasal NO outputs calculated from steady-state plateaux at flows < 1 l/min are substantially smaller than those at flows > 2 l/min. This study aimed to determine the differences in NO output as calculated from the NO concentration plateaux in aspirated nasal air, resulting from different aspiration flows. Nasal NO was determined by chemiluminescent analysis of air obtained from the nasal passages in series during velopharyngeal closure in 8 healthy adults (flows: 0.2-3.7 l/min) and 5 with symptomatic allergic rhinitis (flows: 0.2-3.7 l/min). Mean NO output in the healthy subjects was stable at approximately 315 nl/l/min at flows of 0.2-0.7 l/min, and increased to a second steady output level of approximately 400 nl/l/min (+28%, p < 0.0001) at more physiological flow rates of 2.7 l/min and higher. The symptomatic subjects had substantially higher NO output at all flows (p < 0.001) (709.3 nl/min at 3.7 l/min) than the non-allergic subjects. The flow dependency of the nasal NO output may be explained by failure at low flows for the air stream to penetrate the peripheral parts of the complex nasal passages, and by the presence of a laminar flow regime in which a marginal lamina would tend to insulate the main stream from the mucosa. Thus, previously reported NO outputs obtained at low flows may underestimate nasal NO output compared to output at higher and more physiological transnasal airflow rates, thus affecting interpretation of results.

[Smoking and changes in body weight: can physiopathology and genetics explain this association?].

Tobacco use is the leading preventable cause of death in most countries, including Brazil. Smoking cessation is an important strategy for reducing the morbidity and mortality associated with tobacco-related diseases. An inverse relationship between nicotine use and body weight has been reported, in which body weight tends to be lower among smokers than among nonsmokers. Smoking abstinence results in an increase in body weight for both males and females. On average, sustained quitters gain from 5 to 6 kg, although approximately 10% gain more than 10 kg. Pharmacological treatment for smoking cessation attenuates weight gain. The importance of smoking cessation as a contributing cause of the current obesity epidemic has been little studied. In the USA, the rate of obesity attributable to smoking cessation has been estimated at approximately 6.0 and 3.2% for males and females, respectively. Although the mechanisms are unclear, there is evidence that dopamine and serotonin are appetite suppressants. The administration of nicotine, regardless of the delivery system, acutely raises the levels of these neurotransmitters in the brain, reducing the need for energy intake and consequently suppressing appetite. In addition, nicotine has a direct effect on adipose tissue metabolism, influencing the rate of weight gain following smoking cessation. Leptin, ghrelin and neuropeptide Y are substances that might constitute factors involved in the inverse relationship between nicotine and body mass index, although their roles as determinants or consequences of this relationship have yet to be determined.

Nasal nitric oxide is independent of nasal cavity volume.

This study was performed to evaluate the relationship between nasal nitric oxide (NO) and changes in nasal cavity volume resulting from the topical application of xylometazoline and saline and between upright and supine posture. Nasal NO was measured using a fixed high flow technique that avoids contamination with lower airways NO. In nine healthy subjects nasal NO concentration was measured by a rapid response chemiluminescent analyzer. A tapered tube was inserted in one nostril, into which room air was insufflated to produce a constant flow of 100 ml/second; another tube was inserted into the opposite nostril for NO sampling (air exit side). Subjects were instructed to keep the vellum closed while NO was sampled through a sideport connected to the analyzer. Nasal cavity volume was measured by acoustic rhinometry from a segment of the acoustic pathway, 2 to 5 cm from the nostril. Nasal cavity volume and NO measurements were made at baseline, 15 minutes, and 60 minutes after intervention (administration of saline 0.9%, xylometazoline or posture changes on 3 consecutive days). Xylometazoline produced a significant increase in nasal cavity volume, together with a significant reduction in NO level at 15 and 60 minutes after intervention. In addition, the change from seated to supine position decreased the total nasal volume significantly, but without changes in nasal NO. No correlation was found between the magnitudes of changes in nasal NO and the changes in nasal volume. Topical application of xylomethazoline resulted in increased nasal cavity volume and reduced NO output. In contrast to previous published reports, a technique using high flow rate insufflation demonstrated an abscence of correlation between the magnitudes of changes in nasal NO and nasal cavity volume brought about by decongestant, saline, or posture.

Cotinine as a biomarker of tobacco exposure: development of a HPLC method and comparison of matrices.

Tobacco dependence reaches one-third of the world population, and is the second leading cause of death around the world. Cotinine, a major metabolite of nicotine, is the most appropriate parameter to evaluate tobacco exposure and smoking status due to its higher stability and half-life when compared to nicotine. The procedure involves liquid-liquid extraction, separation on a RP column (Zorbax XDB C(8)), isocratic pump (0.5 mL/min of water-methanol-sodium acetate (0.1 M)-ACN (50:15:25:10, v/v/v/v), 1.0 mL of citric acid (0.034 M) and 5.0 mL of triethylamine for each liter) and HPLC-UV detection (261 nm). The analytical procedure proved to be sensitive, selective, precise, accurate and linear (r>0.99) in the range of 5-500.0 ng/mL for cotinine. 2-Phenylimidazole was used as the internal standard. The LOD was 0.18 ng/mL and the LOQ was 5.0 ng/mL. All samples from smoking volunteers were collected simultaneously to establish a comparison between serum, plasma, and urine. The urinary cotinine levels were normalized by the creatinine and urine density. A significant correlation was found (p<0.01) between all matrices. Results indicate that the urine normalization by creatinine or density is unnecessary. This method is considered reliable for determining cotinine in serum and plasma of smokers and in environmental tobacco smoke exposure.

Quantitative effects of tobacco smoking exposure on the maternal-fetal circulation

BackgroundDespite the existence of various published studies regarding the effects of tobacco smoking on pregnancy, and especially in regards to placental blood flow and vascular resistance, some points still require clarification. In addition, the amount of damage due to tobacco smoking exposure that occurs has not been quantified by objective means. In this study, we looked for a possible association between flow resistance indices of several arteries and the levels of urinary cotinine and the concentration of carbon monoxide in the exhaled air (COex) of both smoking and non-smoking pregnant women. We also looked for a relationship between those findings and fetal growth and birth weight.MethodsIn a prospective design, thirty pregnant smokers and thirty-four pregnant non-smokers were studied. The volunteers signed consent forms, completed a self-applied questionnaire and were subjected to Doppler velocimetry. Tobacco smoking exposure was quantified by subject provided information and confirmed by the measurement of urinary cotinine levels and by the concentration of carbon monoxide in the exhaled air (COex). The weight of newborns was evaluated immediately after birth.ResultsComparing smoking to non-smoking pregnant women, a significant increase in the resistance index was observed in the uterine arteries (P = 0.001) and umbilical artery (P = 0.001), and a decrease in the middle cerebral artery (P = 0.450). These findings were associated with progressively higher concentrations of COex and urinary cotinine. A decrease in the birth weight was also detected (P < 0.001) in association with a progressive increase in the tobacco exposure of the pregnant woman.ConclusionsIn pregnant women who smoke, higher arterial resistance indices and lower birth weights were observed, and these findings were associated with increasing levels of tobacco smoking exposure. The values were significantly different when compared to those found in non-smoking pregnant women. This study contributes to the findings that smoking damage during pregnancy is dose-dependent, as demonstrated by the objective methods for measuring tobacco smoking exposure.

Impact of a Low-Cost and Simple Intervention in Enhancing Treatment Adherence in a Brazilian Asthma Sample

The aim of this study was to evaluate adherence to treatment in persistent asthma in Brazil to determine the factors associated with non-adherence and to measure the efficacy of telephone calls in enhancing adherence. In a prospective, multicenter, interventional clinical trial with parallel groups, asthmatics were randomized into an intervention group or a control group. Asthmatics included in the intervention group received an initial telephone call to record demographic information and asthma characterization. After that, biweekly telephone calls were made to promote treatment adherence. Asthmatics included in the control group received only the initial and final telephone calls. Both groups received three packages of salmeterol/fluticasone for 3 months. The main outcome measure was the percentage of participants who took the prescribed doses of the drug. A total of 271 patients were included. The overall adherence rate was 51.9% for the control group and 74.3% for the intervention group. This meant a reduction of relative risk (RRR) of 47% (p < 0.001). The number needed to treat (NNT) was 4.5. The only variable associated with better adherence was severe persistent asthma. A low-cost easily implemented intervention, tailored to each individual, enhanced the adherence rate among Brazilian asthmatic patients.