Corticosteroid Insensitivity in Smokers with Asthma

Corticosteroids are the most effective treatment for asthma, but the therapeutic response varies considerably between individuals. Several clinical studies have found that smokers with asthma are insensitive to the beneficial effects of short- to medium-term inhaled corticosteroid treatment compared with non-smokers with asthma. It is estimated that 25% of adults in most industrialized countries smoke cigarettes, and similar surveys amongst asthmatic individuals suggest that the prevalence of smoking in this grouping mirrors that found in the general population. Therefore, cigarette smoking is probably the most common cause of corticosteroid insensitivity in asthma. Cigarette smoking and asthma are also associated with poor symptom control and an accelerated rate of decline in lung function. The mechanism of corticosteroid insensitivity in smokers with asthma is currently unexplained but could be due to alterations in airway inflammatory cell phenotypes, changes in glucocorticoid receptor alpha/beta ratio, and/or reduced histone deacetylase activity. Smoking cessation should be encouraged in all smokers with asthma. Short-term benefits include improvements in lung function and asthma control. However, the numbers of sustained quitters is disappointingly small. Additional or alternative drugs need to be identified to treat those individuals who are unable to stop smoking or who have persistent symptoms following smoking cessation.     

The Effect of Cigarette Smoking on the Levels of Nitric Oxide Metabolites in the Sputum of Patients with Acute Asthma

Cigarette smoking may reduce the production of endogenous nitric oxide (NO), which plays an important role in inflammation of the asthmatic airway. NO metabolites in sputum were measured in 11 cigarette smokers and five nonsmokers, all with acute asthma. NO metabolite levels reflected the severity of asthmatic exacerbation, as they were significantly higher in patients with “severe,” or “respiratory arrest imminent” asthma than in patients with “mild” to “moderate” asthma. There were no significant differences in sputum NO metabolite levels between smokers and nonsmokers with asthma, nor were any differences observed in NO metabolite levels for relative cigarette pack-years in smokers. These findings suggest that severe airway inflammation outweighs the effect of smoking on NO in the sputum of patients with asthma.     

The effects of cigarette smoke on airway inflammation in asthma and COPD: therapeutic implications

Asthma and COPD are two chronic inflammatory disorders of the airway characterized by airflow limitation. While many similarities exist between these two diseases, they are pathologically distinct due to the involvement of different inflammatory cells; predominantly neutrophils, CD8 lymphocytes in COPD and eosinophils and CD4 lymphocytes in asthma. Cigarette smoking is associated with accelerated decline of lung function, increased mortality, and worsening of symptoms in both asthma and COPD. Furthermore, exposure to cigarette smoke can alter the inflammatory mechanisms in asthma to become similar to that seen in COPD with increasing CD8 cells and neutrophils and may therefore alter the response to therapy. Cigarette smoke exposure has been associated with a poor response to inhaled corticosteroids which are recommended as first line anti-inflammatory medications in asthma and as an add-on therapy in patients with severe COPD with history of exacerbations. While the main proposed mechanism for this altered response is the reduction of the histone deacetylase 2 (HDAC2) enzyme system, other possible mechanisms include the overexpression of GR-β, activation of p38 MAPK pathway and increased production of inflammatory cytokines such as IL-2, 4, 8, TNF-α and NF-K?. Few clinical trials suggest that leukotriene modifiers may be an alternative to corticosteroids in smokers with asthma but there are currently no drugs which effectively reduce the progression of inflammation in smokers with COPD. However, several HDAC2 enhancers including low dose theophylline and other potential anti-inflammatory therapies including PDE4 inhibitors and p38 MAPK inhibitors are being evaluated.     

Cigarette smoking among asthmatic adults presenting to 64 emergency departments

STUDY OBJECTIVES: The emergency department (ED) is an important focal point for asthmatic individuals with uncontrolled illness. Anecdotally, many adults presenting to the ED with acute asthma are active cigarette smokers. The present study determined the prevalence of cigarette smoking among adults presenting to the ED with acute asthma and identified the factors associated with current smoking status. DESIGN: A prospective cohort study conducted as part of the Multicenter Airway Research Collaboration. PATIENTS: A structured interview was performed in 1,847 patients, ages 18 to 54 years, who presented to the ED with acute asthma. SETTING: Sixty-four EDs in 21 US states and 4 Canadian provinces. RESULTS: Thirty-five percent of the enrolled asthmatic patients were current smokers with a median of 10 pack-years (interquartile range, 4 to 20 pack-years), while 23% were former smokers, and 42% were never-smokers. Current smokers comprised 33% of asthmatic patients aged 18 to 29 years, 40% for ages 30 to 39 years, and 33% for ages 40 to 54 (p < 0.001). In a multivariate analysis, the factors independently associated with current smoking status (p < 0.05) were as follows: age 30 to 39 years; white race/ethnicity; non-high school graduate; lower household income; lack of private insurance; no recent inhaled steroid usage; and no history of systemic steroid usage. Although 50% of current smokers admitted that smoking worsens their asthma symptoms, only 4% stated that smoking was responsible for their current exacerbation. CONCLUSIONS: Although cigarette smoke is generally recognized as a respiratory irritant, cigarette smoking is common among adults presenting to the ED with acute asthma. The ED visit may provide an opportunity for patients to be targeted for smoking cessation efforts.     

Effects of smoking cessation on lung function and airway inflammation in smokers with asthma

RATIONALE: Active smoking in asthma is associated with worsening of symptoms, accelerated decline in lung function, and impaired response to corticosteroids. OBJECTIVES: To examine the short-term effects of smoking cessation on lung function, airway inflammation, and corticosteroid responsiveness in smokers with asthma. METHODS AND MEASUREMENTS: Smokers with asthma were given the option to quit or continue smoking. Both groups underwent spirometry and induced sputum at baseline and at 1, 3, and 6 wk. Cutaneous vasoconstrictor response to topical beclometasone, airway response to oral prednisolone, and sensitivity of peripheral blood lymphocytes to corticosteroids were measured before smoking cessation and at 6 wk. MAIN RESULTS: Of 32 subjects recruited, 11 opted to continue smoking (smoking control group). Of 21 subjects who opted for smoking cessation, 10 quit smoking for 6 wk (quit group). In the comparison of quitters with smokers at 6 wk, the mean (confidence interval [CI]) difference in FEV(1) was 407 ml (21, 793), p = 0.040, and the proportion of sputum neutrophils was reduced by 29 (51, 8), p = 0.039. Total cutaneous vasoconstrictor response score to topical beclometasone improved after smoking cessation with a mean (CI) difference of 3.56 (0.84, 6.28), p = 0.042, between quitters and smokers. There was no change in airway corticosteroid responses after smoking cessation. CONCLUSIONS: By 6 wk after smoking cessation, subjects who quit smoking had achieved considerable improvement in lung function and a fall in sputum neutrophil count compared with subjects who continued to smoke. These findings highlight the importance of smoking cessation in asthma.     

Reduced exhaled breath condensate pH in asthmatic smokers using inhaled corticosteroids

Background and objectives:   Exhaled breath condensate (EBC) pH has been proposed as a biomarker of airway inflammation and oxidative stress in asthma. Cigarette smoking reduces EBC pH in mild asthma. The effects of smoking on EBC pH in more symptomatic asthmatic patients using inhaled corticosteroids (ICS) are unknown. We aimed to compare EBC pH in asthmatic smokers (AS) and non-smokers (ANS) with moderate to severe disease, who were taking ICS. We also investigated the relationship between EBC pH and biomarkers of airway inflammation and oxidative stress.
Methods:   AS ( n  = 18) and ANS ( n  = 17), who were using ICS, were recruited and EBC pH, sputum inflammatory cell counts and sputum supernatant 8-isoprostane concentrations were measured. Full lung function testing was performed.
Results:   EBC pH was significantly lower in AS than in ANS (6.91 vs 7.41). In AS there was a significant inverse correlation between EBC pH and 8-isoprostane levels ( r  = −0.54, P  = 0.03). There was no correlation between EBC pH and sputum neutrophil counts.
Conclusions:   EBC pH appears to be a biomarker of the level of oxidative stress in smokers with moderate to severe asthma. EBC pH may have applications for the longitudinal monitoring of the effects of smoking on the airways of asthmatic patients.     

Smoking Affects Eotaxin Levels in Asthma Patients

Background. Chronic airway inflammation is most important pathological finding in asthma. Cigarette smoking may modify type of inflammation as well as may influence disease severity and response to the treatment. Objective. Thus the aim of this study was to investigate whether cigarette smoking may have an influence on the levels of eotaxin-1, eotaxin-2, eotaxin-3 and IL-5 in patients with stable mild/moderate asthma. Methods. 45 steroid naive asthmatics (mean age: 55.2 ± 2.2 yrs) and 23 “healthy” smokers and non-smokers control subjects (mean age: 54.4 ± 9.7 yrs) were investigated. Asthmatics were divided into two subgroups according to their smoking histories: asthmatic smokers (n = 19) who currently smoke and have a history of > 10 pack-years and asthmatic never-smokers (n = 26). BAL and induced sputum were performed. Cytospins of induced sputum and BAL were stained with May-Grünwald-Giemsa for differential cell counts. Eotaxin-1, eotaxin-2, eotaxin-3 and IL-5 concentrations in serum, sputum and BAL supernatant was measured using a commercial ELISA kit. Results. In sputum supernatant from asthma smokers was significantly higher concentration of eotaxin-1 than in non-smokers asthmatics (203.4 ± 10.0 vs. 140.2 ± 9.5 respectively, p < 0.05). In non-smokers asthma patients levels of BAL eotaxin-1 strongly related to percent and absolute numbers of BAL eosinophils and neutrophils (Rs = 0.737 and Rs = 0.514 respectively, p < 0.05). The number and percent of sputum neutrophils and eosinophils, obtained from smokers asthmatics, significantly correlated with eotaxin-2 concentration in sputum supernatant (Rs = 0.58 and Rs = 0.75 respectively, p < 0.05). IL-5 levels in the serum and sputum from asthmatic never-smokers were significantly higher than they were from asthmatic smokers and “healthy” smokers. Asthmatic never-smokers showed a significantly higher amount of IL-5 in serum and sputum than the asthmatic smokers showed. Conclusions. This study showed the elevated levels of sputum eotaxin-1 as well as serum, sputum and BAL eotaxin-2 in asthmatic smokers without a significant increase of eosinophils compared to asthmatic never-smokers. The eotaxin concentrations were related not only with number of eosinophils but also with the number of neutrophils in all the studied tissue compartments. The data herein permits a suggestion that smoking may influence change in asthmatic airway inflammation by stimulating the production of eotaxins.     

Smoking and airway inflammation in patients with mild asthma.

STUDY OBJECTIVES: Cigarette smoking is common in asthmatic patients, and we investigated the impact of cigarette smoking on airway inflammation in asthma. DESIGN: Single-center observational study of airway inflammation in asthmatic and healthy smokers and nonsmokers. SETTING: Asthma research unit in a university hospital. PATIENTS OR PARTICIPANTS: Sixty-seven asthmatic and 30 nonasthmatic subjects classified as smokers or nonsmokers. Asthmatics had chronic, stable asthma and were not receiving inhaled or oral steroids at the time of the study. INTERVENTIONS: We examined induced-sputum cell counts and levels of interleukin (IL)-8 and eosinophilic cationic protein (ECP). Bronchial hyperreactivity was assessed using methacholine challenge. MEASUREMENTS AND RESULTS: Asthmatic smokers had higher total sputum cell counts than nonsmoking asthmatics and both smoking and nonsmoking healthy subjects. Smoking was associated with sputum neutrophilia in both asthmatics and nonasthmatics (median, 47% and 41%, respectively) compared with nonsmokers (median, 23% and 22%, respectively), and sputum IL-8 was increased in smokers compared with nonsmokers, both in subjects with asthma (median, 945 pg/mL vs 660 pg/mL, respectively) and in healthy subjects (median, 1,310 pg/mL vs 561 pg/mL, respectively). Sputum eosinophils and ECP levels were higher in both nonsmoking and smoking asthmatics than in healthy nonsmokers. In smoking asthmatics, lung function (FEV(1) percent predicted) was negatively related to both sputum IL-8 (r = - 0.52) and sputum neutrophil proportion (r = - 0.38), and sputum IL-8 correlated positively with smoking pack-years (r = 0.57) and percent neutrophil count (r = 0.51). CONCLUSIONS: In addition to the eosinophilic airway inflammation observed in patients with asthma, smoking induces neutrophilic airway inflammation; a relationship is apparent between smoking history, airway inflammation, and lung function in smoking asthmatics.     

慢性阻塞性肺疾病组蛋白去乙酰化酶与糖皮质激素抵抗

慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是一种慢性气道炎症,炎症基因的表达受组蛋白去乙酰化酶(histone deacetylase,HDAC)和组蛋白乙酰化酶(histone acetyltransferase,HAT)调控,通常组蛋白乙酰化增高促进基因转录,降低则抑制基因转录.糖皮质激素(glucocorticoid,GC)的一个重要作用是募集HDAC2到基因表达位点,使基因组蛋白乙酰化程度降低,从而抑制炎症基因表达.由吸烟引起的COPD患者,香烟烟雾氧化应激使得HDAC2减少,降低了GC的抗炎作用,导致GC抵抗,而GC抵抗是COPD抗炎治疗的主要障碍.本文讨论GC抵抗的一些分子机制,为COPD患者治疗方案的制定及改善预后提供理论参考依据.     

Cigarette smoking and ozone-associated emergency department use for asthma by adults in New York City.

The association between ambient ozone (O3) and hospital use for asthma in children and adults is well documented. The question remains of whether there are susceptible subpopulations of asthmatic individuals who are particularly vulnerable to high O3 levels. Because tobacco use was prevalent in our cohort of inner-city adult asthmatic individuals (n = 1,216) in New York City (NYC), we investigated whether cigarette smoking was an effect modifier for asthma morbidity. We examined the relationship between personal tobacco use and O3-associated emergency department (ED) use for asthma in public hospitals in NYC. Three subpopulations were defined: never smokers (0 pack-yr), heavy smokers (>/= 13 pack-yr) and light smokers (< 13 pack-yr). Time-series regression analysis of ED use for asthma and daily O3 levels was done while controlling for temperature, seasonal/long-term trends, and day-of-week effects. Heavy smokers displayed an increased relative risk (RR) of ED visits for asthma in response to increases in 2-d lagged O3 levels (RR per 50 ppb O3 = 1.72; 95% confidence interval: 1.13 to 2.62). Logistic regression analysis confirmed that heavy cigarette use was a predictor of ED use for asthma following days with high O3 levels. Although adverse health effects of ambient O3 have also been documented in asthma populations not using cigarettes (e.g., children), our results suggest that in adult asthmatic individuals, heavy personal tobacco use may be an effect modifier for O3-associated morbidity.     

The role of HDAC2 in cigarette smoke–induced airway inflammation in a murine model of asthma and the effect of intervention with roxithromycin

Background: Cigarette smoke is well known to worsen asthma symptoms in asthmatic patients and to make them refractory to treatment, but the underling molecular mechanism is unclear. We hypothesized that cigarette smoke can reduce the expression of HDAC2 in asthma and the process was achieved by activating the PI3K-δ/Akt signaling pathway. We further hypothesized that roxithromycin (RXM) can alleviate the impacts by cigarette smoke. Methods: A murine model of asthma induced by ovalbumin (OVA) and cigarette smoke has been established. The infiltration of inflammatory cells and inflammatory factors was examined in this model. Finally, we evaluated the expression of HDAC2, Akt phosphorylation levels, and the effects of RXM treatment on the model described earlier. Results: Cigarette smoke exposure reduced HDAC2 protein expression by enhancing the phosphorylation of Akt in PI3K-δ/Akt signaling pathway. Furthermore, RMX reduced the airway inflammation and improved the level of expression of HDAC2 in the cigarette smoke–exposed asthma mice. Conclusions: This study provides a novel insight into the mechanism of cigarette smoke exposure in asthma and the effects of RXM treatment on this condition. These results may be helpful for treating refractory asthma and emphasizing the need for a smoke-free environment for asthmatic patients.     

Bronchial reactivity to cigarette smoke; relation to lung function, respiratory symptoms, serum-immunoglobulin E and blood eosinophil and leukocyte counts

STUDY OBJECTIVES: The aim of the study was to investigate the relationship between the immediate bronchial response to inhaled cigarette smoke [cigarette smoke bronchial reactivity (CBR)] and lung function, respiratory symptoms and markers of allergy and inflammation. DESIGN, PARTICIPANTS AND MEASUREMENTS: This cross-sectional study included 98 smokers. Their lung function and reversibility to inhaled terbutaline was measured. Their clinical history was obtained, an allergological examination was done, and bronchial reactivity to methacholine and inhaled cigarette smoke was measured. Questionnaires about respiratory symptoms, smoking history and drug usage were completed and a blood sample was obtained. Participants were divided into three groups: with asthma, chronic bronchitis and persons without asthma or chronic bronchitis (the respiratory healthy). RESULTS: Forced expiratory volume in 1sec (FEV1) residuals were independently related to the % fall in FEV1 after 12 cigarette smoke inhalations (DFEV%) in all participants (P<001), in asthmatic smokers (P<0.01) and in smokers with chronic bronchitis (P<0.05). In smokers with asthma and chronic bronchitis FEV1 residuals explained 51% and 13% of the variation in DFEV%, respectively, but only 8% (P<0.05) and 1% (N.S.) of the variation in the methacholine bronchial reactivity. In the total population the presence of wheeze (P<0.01), attacks of breathlessness (P<0.05) and daily expectoration (P<0.001) were related to higher DFEV% readings. Serum immunonoglobulin (ES-IgE) was independently related to DFEV% in all participants (P<0.01), in smokers with chronic bronchitis (P<0.01) and in the respiratory healthy (0.05相似文献   

Cigarette Smoking and Asthma Symptom Severity Among Adult Asthmatics

Contrary to what would be expected, smoking habits of asthmatics do not differ from those of the general population: approximately 30% of asthmatic patients smoke cigarettes. Although the relationship between smoking and the incidence of asthma has been well explored, little attention has been paid to documenting the relationship between smoking and asthma symptoms among adults with asthma. The objective of this study was to assess the association of cigarette smoking with asthma symptom severity. The present report is of a cross-sectional study of 225 asthmatics, aged 20-54 years, from six general practice clinics in East Anglia, U.K. The outcome measures are overall asthma symptom score (range 6.3-28) and three asthma symptom domains: respiratory (range 1.3-8), daily activity interference (range 2-8), and physical activity interference (range 3-12), generated from the sum of ordinal responses to questions on asthma symptom severity. Of the sample, 27.0% were current and 22.1% were former smokers. Current smokers more frequently had bothersome asthma symptoms than nonsmokers in both unadjusted analyses and analyses controlling for age, gender, recent visits to the general practitioner for asthma, and asthma medication use (p = 0.06). Respiratory symptoms (p = 0.03) and symptoms that affect daily activities (p = 0.03) were more strongly associated with smoking than symptoms that affect physical activities (p = 0.62). Our data suggest that smoking hastens asthma progression or affects disease control. Increased frequency of symptoms may be an indicator for potential morbidity among asthmatics, especially those who smoke cigarettes. The hazards associated with smoking among asthmatics need to be more clearly emphasized by physicians and public health officials in order to convince people with asthma who smoke to stop.     

Acute effects of passive smoking on lung function and airway reactivity in asthmatic subjects

We studied the acute effects of one hour of passive cigarette smoking on the lung function and airway reactivity of nine young adult asthmatic volunteers. At the time of this study, the subjects were asymptomatic and had normal or nearly normal lung function. Passive smoking produced no change in expiratory flow rates. However, there was a small decrease in nonspecific bronchial reactivity, as assessed by methacholine inhalation challenge testing (p = 0.022). Pharmacologically active substances present in cigarette smoke, such as nicotine, may explain the observed change in airway reactivity. Although the finding of decreased airway reactivity might suggest that passive smoking produces a "protective" effect on the underlying asthma, the observed change in reactivity was slight and of uncertain clinical significance. We conclude that passive smoking presents no acute respiratory risk to young asymptomatic asthmatic patients.     

Mechanisms of chronic airway obstruction in smokers

Studies over the past few decades have showed a clear association between cigarette smoking and the development of chronic airway obstruction. Yet, only a minority of smokers is affected so that in many, even heavy, smokers, pulmonary function remains within normal limits. While carcinogens have been well characterized, there is only limited information about the constituents of cigarette smoke responsible for inducing chronic airway obstruction. In addition, the associated risks factors for airway obstruction in smokers have not been totally identified. The present paper is a review of the recently accumulated facts concerning the intimate action of cigarette smoke at the level of large and small airways and lung parenchyma. The role of classical inflammatory cells such as neutrophils and alveolar macrophages is reviewed, but emphasis is put on recent evidence indicating the involvement of CD8 + T-lymphocytes and possibly eosinophils in the genesis of the structural changes leading to airways obstruction. The mechanisms by which airway inflammation and remodelling cause airway narrowing and airflow limitation are discussed, along with the associated loss of lung elasticity secondary to destructive emphysema. Other biological, epidemiological, physiopathological, and clinical aspects are analyzed, stressing such fundamental aspects as the defence mechanisms, the morpho-functional correlations, the identification of susceptible smokers, and the early detection of airway obstruction, both in specialized laboratories and in primary care.     

Influence of C-159T SNP of the CD14 gene promoter on lung function in smokers

CD14, a co-receptor for endotoxin, plays a significant role in regulating the inflammatory response to this agent. The C-159T single nucleotide polymorphism (SNP) in the CD14 gene promoter is an important regulator of CD14 expression, with TT homozygotes having increased expression of CD14. This SNP has been linked to pathogenesis of asthma and with cardiovascular diseases in smokers. We hypothesize that CD14 also plays a role in the pathophysiology of COPD in smokers who are exposed to endotoxin contained in cigarette smoke as well as endotoxin derived from Gram-negative microbes colonizing their airways. To assess the effect of the C-159T SNP of the CD14 gene promoter on lung function, we recruited 246 smokers 40 years of age or older with a range of 10–156 pack-year smoking exposures. The TT genotype was associated with lower lung function in smokers with a moderate smoking history. However, the CC genotype was associated with decreased lung function in heavy smokers (>56 pack years). The effect of CC genotype on severity of COPD is analogous with the effect of this genotype in risk for asthma. CD14 may be a factor in the pathophysiology of COPD, as it is in asthma and smoking-related cardiovascular diseases.     

Smoking-related beliefs and behaviour among adults with asthma in a representative population sample

Background: Smoking and exposure to environmental tobacco smoke are inadvisable for adults with asthma.
Aims: To determine the smoking prevalence and daily smoking rate of asthmatics and compare smoking-related beliefs and behaviours among smokers with and without asthma. To compare beliefs of asthmatics about passive smoking and asthma, how many are exposed at home and what they do when they are exposed, with people who do not have asthma.
Methods: A representative population survey of 3019 South Australian adults aged 15 years and older interviewed in their own homes in late 11992.
Results: Twenty-eight per cent of asthmatics were smokers; mean daily smoking rate was 17.6. Asthmatics had similar patterns of smoking, readiness to quit and quit attempt histories as people without asthma. More than 40% of smokers with asthma did not perceive that smoking had greatly affected their health, over half did not believe they were at risk in future and two-thirds did not think future health problems would be serious. Among non-smokers, despite being more convinced of the effects of passive smoking on asthma, and being more concerned about exposure, those with asthma were no more likely to take protective action in response to actual or imminent exposure than those without asthma. One in ten non-smokers with asthma were exposed to smoking at home.
Conclusions: The smoking habits of adults with asthma are cause for concern, with many asthmatic smokers perceiving they are not personally at risk from their smoking. Health education principles should be used by health professionals caring for asthmatic smokers to guide the selection and delivery of smoking cessation strategies. Prevailing restrictions on indoor smoking play an important role in protecting the respiratory health of non-smokers with asthma.     

Smoking pattern of smokers with and without tobacco-smoke-related lung diseases

The number of cigarettes smoked, the duration of the smoking habit, and the tar content of the smoke influence the occurrence of tobacco-smoke-related lung diseases, as may also patterns of smoke inhalation. We therefore determined the smoking pattern, especially the time relation between cigarette puff and inhalation, in smokers with and without tobacco-smoke-related lung diseases. On the basis of clinical and radiologic findings as well as pulmonary function tests, 91 smokers were classified as smokers without lung disease, with small airway disease, with simple chronic bronchitis, with obstructive bronchitis, with pulmonary emphysema, and with lung cancer. Smoking and breathing patterns were recorded, using a smoke-flow machine and a strain-gauge belt while the subject smoked a cigarette. Blood levels of COHb were determined before and after smoking. Of the smoking characteristics assessed, puff-inhalation time, puff peak pressure, and the venous difference in COHb level before and after smoking varied significantly among the smoker groups. Puff-inhalation time, reflecting the duration of smoke retention in the mouth, was only 0.08 s (i.e., practically zero) in smokers with pulmonary emphysema and differed significantly from the time in the other groups. This puffing characteristic may be the consequence or the cause of emphysema. If the latter is true, smokers with emphysema may perhaps lack the acute airway response to smoke inhalation that normally protects most smokers from immediately inhaling tobacco smoke.