Area of residence, birthplace, and asthma in Puerto Rican children

RATIONALE: Puerto Ricans have the highest prevalence of asthma among all ethnic groups in the United States. There have been no studies that directly compare the burden of asthma between Puerto Ricans living in Puerto Rico and those living in the mainland United States. OBJECTIVE: To examine the relation between birthplace, area of residence, and asthma in Puerto Rican children. METHODS: Multistage population-based probability sample of children in the San Juan and Caguas metropolitan areas in Puerto Rico and in the Bronx, NY. Information was collected in a household survey of 2,491 children and their primary caretakers. RESULTS: The overall prevalence of asthma among Puerto Rican children in this study was very high (38.6%). Although children from Puerto Rico had higher socioeconomic status and lower rates of premature birth and prenatal smoke exposure, the prevalence of lifetime asthma was higher in Puerto Rican children living in Puerto Rico than in Puerto Rican children living in the South Bronx (41.3% vs 35.3%, p = 0.01). In multivariable analysis, residence in Puerto Rico was associated with increased odds of lifetime asthma (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.03 to 1.57) and lifetime hospitalization for asthma (OR, 1.47; 95% CI, 1.04-2.07). CONCLUSIONS: Puerto Rican children in Puerto Rico had a higher risk of asthma than Puerto Rican children in the South Bronx, highlighting the need for further examination of the roles of migration, acculturation, and environmental and psychosocial factors on the development of asthma in this high-risk population.     

FEV1 performance among patients with acute asthma: results from a multicenter clinical trial

OBJECTIVE: To determine the ability of patients seen for acute asthma exacerbations in the emergency department (ED) to perform good-quality FEV(1) measurements. METHODS: Investigators from 20 EDs were trained to perform spirometry testing as part of a clinical trial that included standardized equipment with special software-directed prompts. Spirometry was done on ED arrival and 30 min, 1 h, 2 h, and 4 h later, and during follow-up outpatient visits. MEASUREMENTS: Study performance criteria differed from American Thoracic Society (ATS) guidelines because of the population acuity and severity of illness as follows: ability to obtain acceptable FEV(1) measures (defined as two or more efforts with forced expiratory times >/= 2 s and time to peak flow < 120 ms or back-extrapolated volume < 5% of the FVC) and reproducibility criteria (two highest acceptable FEV(1) values within 10% of each other). RESULTS: Of the 620 patients (age range, 12 to 65 years), > 90% met study acceptability criteria on ED arrival and 74% met study reproducibility criteria. Mean initial FEV(1) was 38% of predicted. Spirometry quality improved over time; by 1 h, 90% of patients met study acceptability and reproducibility criteria. Patients with severe airway obstruction (FEV(1) < 25% of predicted) were initially less likely to meet quality goals, but this improved with time. The site was also an independent predictor of quality. CONCLUSION: When staff are well trained and prompt feedback regarding adequacy of efforts is given, modified ATS performance goals for FEV(1) tests can be met from most acutely ill adolescent and adult asthmatics, even within the first hour of evaluation and treatment for an asthma exacerbation.     

Effect of pet removal on pet allergic asthma

BACKGROUND: Allergen avoidance has been recommended in the management of allergic asthma. Very few studies have assessed the effect of pet removal on pet allergic asthma. OBJECTIVE: We examined the effect of pet removal from homes on pulmonary function testing, airway hyperresponsiveness, and medication use. DESIGN: Prospective, nonrandomized, nonblinded observational study. PATIENTS AND METHODS: Subjects included 20 symptomatic patients with newly diagnosed pet allergic asthma who were keeping domestic animals, including hamsters, cats, dogs, and ferrets, and were sensitized to the animals. They were treated with inhaled corticosteroids or other medications according to recommendations by level of severity of the Global Initiative for Asthma. Methacholine inhalation tests were performed regularly before and after starting medication. Clinical features were compared between the patients who gave away their pets according to recommendations by the clinician (removal group) and the patients who refused to give away their pets (keeping group). RESULTS: There were 10 patients in both the removal group and the keeping group. After >or= 1 year of follow-up with or without pet removal, a 5.9-fold increase in the provocative concentration of methacholine causing a 20% fall in FEV(1) was observed in the removal group compared with a 2.3-fold increase in the keeping group (p = 0.04). There were no significant differences in the changes in FEV(1) and peak flow variability. Finally, no patient received inhaled corticosteroids in the removal group, whereas all but one of the patients needed beclomethasone dipropionate (mean dose, 600 mug/d) in the keeping group. CONCLUSION: This study indicates that removal of pets from homes reduces airway responsiveness in patients with pet allergic asthma more than optimal pharmacotherapy alone, thereby enabling a decrease in inhaled corticosteroid doses.     

Differences in airway cytokine profile in severe asthma compared to moderate asthma

BACKGROUND: Some studies of severe asthma suggest that persistence or alteration in the pattern of inflammation may be associated with the severity of the disease. Whether there are differences in the expression of the principal cytokines and chemokines relevant to eosinophilic and neutrophilic inflammation in the airway tissues of severe compared to moderate asthmatics has not been determined. The aim of this study was to compare the patterns of expression of representative T-helper (Th) type 1 (interferon [IFN]-gamma) and Th-2 cytokines (interleukin [IL]-4, IL-5) and the neutrophil- and eosinophil-associated chemokines (IL-8 and eotaxin) in the airway tissues of patients with severe and moderate asthma. METHODS: Subjects with severe asthma (n = 24) and a comparison moderate asthma group (n = 26) were assessed using spirometry, induced sputum, exhaled nitric oxide, and bronchial biopsy. The expression of proteins of interest in the epithelium and subepithelium of the airway wall was examined by immunocytochemistry. RESULTS: Subjects with severe asthma were more symptomatic, had a lower FEV(1), and had more sputum neutrophilia (p = 0.007) and eosinophilia (p = 0.001). Exhaled nitric oxide was similar between groups. IL-8 and IFN-gamma expression were increased and IL-4 expression was decreased in severe asthma compared to moderate disease (p < 0.001 for each comparison). Eotaxin and IL-5 expression did not differ between the groups. CONCLUSION: Patients with severe asthma have increases in neutrophils and eosinophils in the sputum, and differ in airway cytokine/chemokine expression from moderate asthmatics. Excess neutrophilia may be explained by increased expression of IL-8, but differences in eosinophilia do not appear to be associated with IL-5 and eotaxin expression.     

Bronchial hyperresponsiveness, airway inflammation, and airflow limitation in endurance athletes

BACKGROUND: Whereas a high prevalence of bronchial abnormalities has been reported in endurance athletes, its underlying mechanisms and consequences during exercise are still unclear. STUDY OBJECTIVES: The purpose of this study was to assess the following: (1) bronchial responsiveness to methacholine and to exercise; (2) airway inflammation; and (3) airflow limitation during intense exercise in endurance athletes with respiratory symptoms. DESIGN: Cross-sectional observational study. SETTING: Lung function and exercise laboratory at a university hospital. PATIENTS AND MEASUREMENTS: Thirty-nine endurance athletes and 13 sedentary control subjects were explored for the following: (1) self-reported respiratory symptoms; (2) bronchial hyperresponsiveness (BHR) to methacholine and exercise; (3) airflow limitation during intense exercise; and (4) bronchial inflammation using induced sputum and nitric oxide (NO) exhalation. RESULTS: Fifteen athletes (38%) showed BHR to methacholine and/or exercise in association with bronchial eosinophilia (mean [+/- SD] eosinophil count, 4.1 +/- 8.5% vs 0.3 +/- 0.9% vs 0%, respectively), higher NO concentrations (19 +/- 10 vs 14 +/- 4 vs 13 +/- 4 parts per billion, respectively), a higher prevalence of atopy, and more exercise-induced symptoms compared with non-hyperresponsive athletes and control subjects (p < 0.05). Furthermore, airflow limitation during intense exercise was observed in eight athletes, among whom five had BHR. Athletes with airflow limitation reported more symptoms and had FEV1, FEV1/FVC ratio, and forced expiratory flow at midexpiratory phase values of 14%, 9%, and 29%, respectively, lower compared with those of nonlimited athletes (p < 0.05). CONCLUSION: BHR in endurance athletes was associated with the criteria of eosinophilic airway inflammation and atopy, whereas airflow limitation during exercise was primarily a consequence of decreased resting spirometric values. Both BHR and bronchial obstruction at rest with subsequent expiratory flow limitation during exercise may promote respiratory symptoms during exercise in athletes.     

Absence of relationships between tuberculin responses and development of adult asthma with rhinitis and atopy

OBJECTIVE: To investigate the relationship between tuberculin skin responses and the development of adult asthma, rhinitis, and atopy. METHODS: Two hundred fourteen patients with mild-to-moderate asthma accompanied with rhinitis and 220 normal volunteers underwent a medical history, chest radiography, allergen skin-prick testing (SPT), bovine Mycobacterium tuberculosis vaccine (BCG) scar identification, purified protein derivative (PPD) tuberculin skin testing, serum-total and serum-specific IgE measurements, and bronchial provocation (provocative dose of histamine causing a 20% fall in FEV(1) [PD(20)]). RESULTS: Thirty-one normal volunteers (14.1%) and 168 asthma-rhinitis subjects (78.5%) had one or more positive skin test results (p < 0.0001). Neither the presence of a BCG scar nor a history of BCG vaccination had a significant effect on atopy in either group. The rate of PPD positivity had no statistical difference between atopy and nonatopy in both groups. In multivariate logistic regression analysis, the odds ratio for tuberculin reactivity was not related to the level of serum-total IgE nor to the level of serum-specific IgE to Dermatophagoides pteronyssinus (DP) and Dermatophagoides farinae (DF), skin response to DP and DF, and PD(20). Overall, no significant correlations were found between tuberculin skin reactivity and log serum-total IgE or PD(20). CONCLUSION: There is no relationship between history of tuberculosis infection, tuberculin responses, and development of adult bronchial asthma, allergic rhinitis, and atopy. Our study suggests that the protection provided by intradermal BCG vaccination in infants to prevent atopic diseases may be limited in early childhood, when a substantial memory of cellular immune modulation still exists.     

Spirometric criteria for airway obstruction: Use percentage of FEV1/FVC ratio below the fifth percentile, not < 70%

BACKGROUND: Current authoritative spirometry guidelines use conflicting percentage of FEV1/FVC ratios (FEV1/FVC%) to define airway obstruction. The American Thoracic Society/European Respiratory Society Task Force characterizes obstruction as a FEV1/FVC% below the statistically defined fifth percentile of normal. However, many recent publications continue to use the Global Initiative for Chronic Obstructive Lung Disease (GOLD) primary criterion that defines obstruction as a FEV1/FVC% < 70%. Data from the Third National Health and Nutrition Examination Survey (NHANES-III) should identify and quantify differences, help resolve this conflict, and reduce inappropriate medical and public health decisions resulting from misidentification. METHODS: Using these two guidelines, individual values of FEV1/FVC% were compared by decades in 5,906 healthy never-smoking adults and 3,497 current-smokers of black (African American), Hispanic (Latin), or white ethnicities aged 20.0 to 79.9 years. RESULTS: In the never-smoking population, the lower limits of normal used in other reference equations fit reasonably well the NHANES-III statistically defined fifth percentile guidelines. But nearly one half of young adults with FEV1/FVC% below the NHANES-III fifth percentile of normal were misidentified as normal because their FEV1/FVC% was > 70% (abnormals misidentified as normal). Approximately one fifth of older adults with observed FEV1/FVC% above the NHANES-III fifth percentile had FEV1/FVC% ratios < 70% (normals misidentified as abnormal). CONCLUSIONS: The GOLD guidelines misidentify nearly one half of abnormal younger adults as normal and misidentify approximately one fifth of normal older adults as abnormal.     

Persistent airway obstruction after virus infection is not associated with airway inflammation

BACKGROUND: This study examined the contribution of airway inflammation to the delayed lung function recovery that occurs in some people following virus-induced asthma exacerbations. METHODS: Subjects (n = 40) were recruited at hospital admission for acute asthma exacerbation. Respiratory virus infection was diagnosed by viral nucleic acid detection and/or cell culture, using induced sputum, nasal, or throat swabs. Data collected included lung function, answers to common cold and asthma control questionnaires, and induced sputum cellular profiles. Subjects were reexamined 4 to 6 weeks postexacerbation and were compared with stable asthmatic subjects (n = 26) who had been recruited from ambulatory care clinics. RESULTS: Persistent airway obstruction, defined as lung function improvement at follow-up (ie, change in FEV1 percent predicted [Delta%FEV1]) of <15%, was observed in 10 subjects (25%). Airway recovery (Delta%FEV1, > or = 15%) was observed in the remaining subjects (30 subjects; 75%). During the acute episode, the airway-recovery group had increased total cell count (p = 0.019), increased number of neutrophils (p = 0.005), and increased percentage of neutrophils (p = 0.0043) compared to the group of stable subjects with asthma. Postexacerbation, the airway-recovery group had reduced numbers of neutrophils and an increased percentage of eosinophils. In contrast, during exacerbation, subjects with persistent airway obstruction showed no differences in inflammatory cell counts compared to stable subjects with asthma, nor did cell counts change postexacerbation. Symptoms improved in both groups postexacerbation. However, in the persistent-airway-obstruction group, asthma remained uncontrolled. CONCLUSION: Persistent airway obstruction and uncontrolled asthma are observed in some people after viral asthma exacerbations. These abnormalities are not associated with inflammatory cell influx into the airway lining fluid during the exacerbation and may reflect the involvement of noncellular elements. Further work should explore other mechanisms leading to incomplete airway recovery.     

Diagnostic classification of persistent rhinitis and its relationship to exhaled nitric oxide and asthma: a clinical study of a consecutive series of patients

BACKGROUND: Rhinitis and asthma represent the manifestation of one syndrome. Our hypothesis is that in patients with symptoms of persistent rhinitis, lower airway inflammation, lower respiratory symptoms, and lung function abnormalities compatible with asthma are more frequently associated with the diagnosis of allergic rhinitis (AR) and chronic rhinosinusitis (CRS) than with nonallergic rhinitis (NAR). METHODS: One hundred eight of 590 consecutive patients referred in 1 year for rhinitis were enrolled on the basis of nasal symptoms lasting > 4 weeks. Asthma was diagnosed on the basis of symptoms and a positive bronchodilation testing result and/or methacholine hyperresponsiveness. Exhaled nitric oxide (Feno) was measured with the single exhalation method at 50 mL/s. RESULTS: AR was diagnosed in 39%, NAR in 21%, and CRS in 40%. The prevalence of asthma was significantly higher in AR patients (33%) and CRS patients (42%) than in NAR patients (8.7%) [p = 0.036 and p = 0.005, respectively]. Feno was significantly higher in patients with AR and CRS compared to patients with NAR (44.3 parts per billion [ppb]; 95% confidence interval [CI], 34 to 54 ppb; and 53 ppb; 95% CI, 42 to 64 ppb; vs 22 ppb; 95% CI, 18 to 27 ppb; p = 0.002 and p = 0.001, respectively). Patients with asthma had Feno values significantly higher than patients without asthma (64 ppb; 95% CI, 51 to 77 ppb; vs 33.3 ppb; 95% CI, 28 to 39 ppb; p < 0.001). CONCLUSIONS: The diagnostic classification of persistent rhinitis helps to predict lower airway inflammation (increased Feno) and prevalence of asthma: AR and CRS are associated with higher mean Feno values and higher prevalence of asthma than NAR.     

Tiotropium and simplified detection of dynamic hyperinflation

STUDY OBJECTIVE: To detect dynamic hyperinflation (DH) by evaluating reduction in inspiratory capacity (IC) during metronome-paced hyperventilation (MPH) in patients with moderate-to-severe COPD, studied before and after treatment with tiotropium. METHODS: IC and FEV(1) were measured before and immediately after MPH at two times resting the respiratory rate for 20 s in 60 COPD patients (28 men; mean age, 66 +/- 10 years [+/- SD]) before and after 30 days of treatment with tiotropium bromide, 18 mug. Patients were encouraged to maintain a constant tidal volume during MPH. RESULTS: At baseline, mean FEV(1) was 1.5 +/- 0.1 L (+/- SE) [57 +/- 1.6% of predicted], mean FVC was 2.6 +/- 0.1L (77 +/- 1.8% of predicted), and mean FEV(1)/FVC was 56 +/- 1%. After 180 mug of aerosolized albuterol sulfate, mean FEV(1) was 1.7 +/- 0.1 L (63 +/- 1.5% of predicted) [p < 0.001] and mean FEV(1)/FVC was 58 +/- 1%. Compared to baseline, after 30 days and 1.5 h after tiotropium there was an increase in IC of 0.18 +/- 0.04L (p < 0.0001); FEV(1) of 0.13 +/- 0.03 L (5.6 +/- 0.8% of predicted; p = 0.0002); FVC of 0.22 +/- 0.05 L (6.5 +/- 1.3% of predicted; p < 0.001); and decrease in end-expiratory lung volume (EELV)/total lung capacity (TLC) of - 3.1 +/- 0.6% (p = 0.0001); a decrease in end-inspiratory lung volume (EILV)/TLC of - 2.9 +/- 1.3% (p = 0.03); and no change in TLC (- 0.06 +/- 0.05 L). Results following MPH-induced DH at baseline and after 30 days of tiotropium were similar, with decreases in IC (- 0.35 +/- 0.03 L; p < 0.001); FEV(1) (- 0.05 +/- 0.04 L; p = 0.2); and FVC (- 0.22 +/- 0.03 L; p < 0.0001); no change in TLC; and increases in EELV/TLC (11.8 +/- 1.0% of predicted; p < 0.0001) and EILV/TLC (4.0 +/- 1.3% of predicted, p < 0.003). CONCLUSION: In patients with moderate-to-severe COPD, tiotropium did not reduce MPH-induced DH and reduction in IC, compared to baseline. However, because tiotropium induced bronchodilation and increased baseline IC, lower operational lung volumes may blunt the effect of MPH-induced DH. The noninvasive simplicity of MPH-induced DH provides a clinically useful screening surrogate to monitor changes in IC following treatment with tiotropium.     

FEV1/FEV6 and FEV6 as an alternative for FEV1/FVC and FVC in the spirometric detection of airway obstruction and restriction

STUDY OBJECTIVES: To evaluate the use of the FEV(1)/forced expiratory volume at 6 s of exhalation (FEV(6)) ratio and FEV(6) as an alternative for FEV(1)/FVC and FVC in the detection of airway obstruction and lung restriction, respectively. SETTING: Pulmonary function laboratory of the Academic Hospital of the Free University of Brussels. PARTICIPANTS: A total of 11,676 spirometric examinations were analyzed on subjects with the following characteristics: white race; 20 to 80 years of age; 7,010 men and 4,666 women; and able to exhale for at least 6 s. METHODS: Published reference equations were used to determine lower limits of normal (LLN) for FEV(6), FVC, FEV(1)/FEV(6), and FEV(1)/FVC. We considered a subject to have obstruction if FEV(1)/FVC was below its LLN. A restrictive spirometric pattern was defined as FVC below its LLN, in the absence of obstruction. From these data, sensitivity and specificity of FEV(1)/FEV(6) and FEV(6) were calculated. RESULTS: For the spirometric diagnosis of airway obstruction, FEV(1)/FEV(6) sensitivity was 94.0% and specificity was 93.1%; the positive predictive value (PPV) and negative predictive value (NPV) were 89.8% and 96.0%, respectively. The prevalence of obstruction in the entire study population was 39.5%. For the spirometric detection of a restrictive pattern, FEV(6) sensitivity was 83.2% and specificity was 99.6%; the PPVs and NPVs were 97.4% and 96.9%, respectively. The prevalence of a restrictive pattern was 15.7%. Similar results were obtained for male and female subjects. When diagnostic interpretation differed between the two indexes, measured values were close to the LLN. CONCLUSIONS: The FEV(1)/FEV(6) ratio can be used as a valid alternative for FEV(1)/FVC in the diagnosis of airway obstruction, especially for screening purposes in high-risk populations for COPD in primary care. In addition, FEV(6) is an acceptable surrogate for FVC in the detection of a spirometric restrictive pattern. Using FEV(6) instead of FVC has the advantage that the end of a spirometric examination is more explicitly defined and is easier to achieve.     

Targeting airway inflammation in asthma: current and future therapies

Asthma is a chronic inflammatory disease of the airway that requires long-term antiinflammatory therapy. Inhaled corticosteroids (ICSs) are recommended for first-line treatment of persistent disease, but not all patients achieve asthma control even when these agents are used in high doses and in combination with other medications, including a long-acting beta(2)-agonist or a leukotriene modifier. Such patients may require additional therapy. As information about asthma pathophysiology and inflammatory phenotypes continues to increase, and additional antiinflammatory options become available, it may be possible to target antiinflammatory therapy to various aspects of the disease and consequently to improve the treatment of patients with inadequate responses to standard ICS-based therapy. Several novel antiinflammatory therapies are in different stages of clinical development. The most clinically advanced of these is omalizumab, a recombinant humanized monoclonal antibody that specifically targets IgE and is indicated for patients with moderate-to-severe asthma caused by allergies. Omalizumab has demonstrated efficacy in patients with moderate-to-severe asthma and documented evidence of allergen sensitivity. Other key therapy options in clinical development either target proinflammatory cytokines (eg, interleukin-4 and tumor necrosis factor-alpha) or inflammatory cells (eg, T-helper type 2 cells and eosinophils). This review provides an overview of the current and future approaches targeting airway inflammation in patients with asthma.     

Diagnostic tests for asthma in firefighters

BACKGROUND: Subjects with asthma do not meet medical requirements for professions such as firefighting. OBJECTIVE: To prospectively determine the diagnostic value of respiratory symptoms and various tests used in the assessment of asthma in a cohort of firefighters. METHODS: A questionnaire, spirometry, direct and indirect airway challenge tests, exhaled nitric oxide, and skin-prick tests were administered prospectively to 101 of 107 firefighters employed in Basel, Switzerland. Asthma was defined as the combination of respiratory symptoms with airway hyperresponsiveness. RESULTS: Six of 101 firefighters (6%) had physician-diagnosed asthma, which could be confirmed in 4 firefighters. In contrast, asthma was diagnosed in 14% (14 of 101 firefighters). Wheezing was the most sensitive symptom for the diagnosis of asthma (sensitivity, 78%; specificity, 93%). Other respiratory symptoms showed a higher specificity than wheezing but a markedly lower sensitivity. Bronchial airway challenge with mannitol was the most sensitive (92%) and specific (97%) diagnostic test for asthma. Using a cutoff point of 47 parts per billion, nitric oxide had a similar specificity (96%) but lower sensitivity (42%) compared to the direct (methacholine) and indirect (mannitol) airway challenge tests. CONCLUSION: Asthma was considerably underdiagnosed in firefighters. The combination of a structured symptom questionnaire with a bronchial challenge test allows to identify patients with asthma and should routinely be used in the assessment of active firefighters and may be of help when evaluating candidates for this profession.     

The effect of montelukast on bronchial hyperreactivity in preschool children

INTRODUCTION: The effect of montelukast therapy on bronchial hyperreactivity (BHR) as measured by the methacholine challenge test in preschool children has not yet been reported. OBJECTIVE: To determine the effect of montelukast (4 mg/d) on BHR as evaluated by a provocative concentration of a substance causing a 20% fall in FEV(1) (PC(20)) values in preschool asthmatic children. PATIENTS: A total of 26 preschool children (8 girls) aged 3.3 to 6.0 years (mean [+/- SD] age, 4.7 +/- 0.8 years) with mild asthma. DESIGN: Double-blind randomized, placebo controlled, crossover study. Each child received 4 weeks of treatment with 4 mg of either montelukast or placebo separated by a 2-week washout period. Primary outcomes were PC(20) values and the stage number (triple dose) at which FEV(1) values dropped by 20%(.) Post-montelukast therapy PC(20) was compared to those for the post-placebo period. RESULTS: Following 4 weeks of montelukast treatment, the mean PC(20) was 4.79 +/- 4.69 mg/mL, while after 4 weeks of placebo the mean PC(20) was 2.07 +/- 2.37 mg/mL (p = 0.001). The montelukast/placebo ratio for PC(20) was 2.56 with a 95% confidence interval (CI) of 1.71 to 3.99. The median difference in stage was one triple dose with a 95% CI of 0.5 to 1.5. CONCLUSIONS: Four weeks of treatment with montelukast resulted in a decreased BHR compared with placebo.     

Exhaled nitric oxide concentration is affected by age, height, and race in healthy 9- to 12-year-old children

BACKGROUND: The fractional concentration of exhaled nitric oxide (Feno) is a useful indicator of airway inflammation in children and adults with asthma. METHODS: We determined the range of Feno concentrations and the factors affecting it in a large sample of healthy school children attending grades 4 through 6, in Windsor, ON, Canada. RESULTS: Feno was measured in 657 children between 9.1 and 12.9 years of age. The range of Feno concentrations in healthy school children was 12.7 parts per billion (ppb) [95% confidence interval (CI), 11.8 to 13.7 ppb] in whites and 22.8 ppb [95% CI, 17.9 to 27.7 ppb] in Asian-Canadian children (p < 0.001). Feno values also appeared to be higher in African-Canadian children than in whites, although the CI was wide because of the small number of African-Canadian children sampled. Feno rose slightly but significantly with age (p = 0.007) and with height (p = 0.023). Body mass index and gender did not significantly alter the measured Feno. FVC had a nonsignificant effect on Feno. Participation in physical activity during the same day had a borderline-significant effect on measured Feno, but a reported history of a respiratory tract infection in the preceding 2 weeks did not. CONCLUSIONS: Feno concentrations in healthy school-aged children appeared to be affected by race, and, to a lesser extent, by age and height. These factors should be taken into consideration when interpreting clinical results.     

The incidence of asthma in young adults

STUDY OBJECTIVES: Longitudinal data on adult asthma are sparse. The objectives of this study were to determine the incidence of asthma and to establish the risk factors for the development of asthma in subjects who were 12 to 41 years old over an 8-year period. DESIGN: From birth cohorts over the period 1953 to 1982 in The Danish Twin Registry, 19,349 subjects with no history of asthma, as determined by a questionnaire-based survey in 1994, answered a follow-up questionnaire in 2002. The subjects were regarded as incident asthma cases when answering "yes" to the question "Do you have, or have you ever had asthma?" in 2002, and "no" to the same question in 1994. RESULTS: A total of 838 cases (4.3%) of new asthma were identified in 2002. The incidence rates of asthma were 4.5 and 6.4 per 1,000 person-years, respectively, among male and female subjects. For all ages, the probability of adult-onset asthma was greater for female subjects (odds ratio [OR], 1.49; p < 0.001), and for both sexes there was a slow decline in probability with increasing age. There was a positive association between increasing body mass index (BMI) and risk of adult-onset asthma applying to both sexes (OR, 1.05 per unit; p < 0.001). Furthermore, positive associations were found between incident asthma and a history of hay fever (OR: male subjects, 4.2; female subjects, 3.7; p < 0.001), eczema (OR: male subjects, 3.5; female subjects, 2.0; p < 0.001), and both (OR: male subjects, 6.9; female subjects, 8.0; p < 0.001). CONCLUSIONS: There is a continuing high incidence of asthma past childhood that is most pronounced among female subjects. Increasing levels of BMI are associated with a greater likelihood of developing asthma for both sexes. A substantial portion of cases of adult asthma is preceded by upper airway allergic symptoms and/or eczema, thus indicating a shared pathogenesis.     

Tiotropium bromide inhibits relapsing allergic asthma in BALB/c mice

Recurrent relapses of allergic lung inflammation in asthmatics may lead to airway remodeling and lung damage. We tested the efficacy of tiotropium bromide, a selective long-acting, muscarinic receptor antagonist as an adjunct therapy in relapses of allergic asthma in mice. We compared the effectiveness of local intranasal administration of tiotropium and dexamethasone in acute and relapsing allergic asthma in BALB/c mice. Although tiotropium at low doses is a potent bronchodilator, we tested higher doses to determine effectiveness on inflammation and mucus hypersecretion. A 5-day course of twice daily intranasal tiotropium or dexamethasone (1 mg/kg (b.w.)) suppressed airway eosinophils by over 87% during disease initiation and 88% at relapse compared to vehicle alone. Both drugs were comparable in their capacity to suppress airway and parenchymal inflammation and mucus hypersecretion, though tiotropium was better than dexamethasone at reducing mucus secretion during disease relapse. Despite treatment with either drug, serum antigen-specific IgE or IgG1 antibody titres remained unchanged. Our study indicates that tiotropium at higher doses than required for bronchodilation, effectively suppresses inflammation and mucus hypersecretion in the lungs and airways of mice during the initiation and relapse of asthma. Tiotropium is currently not approved for use in asthma. Clinical studies have to demonstrate the efficacy of tiotropium in this respiratory disease.     

Alveolar nitric oxide and effect of deep inspiration during methacholine challenge

STUDY OBJECTIVES: To assess whether the dual anatomic origin of exhaled nitric oxide (NO), namely alveolar and bronchial, could explain the link between exhaled NO and airway responsiveness, and could participate in the bronchodilatory effect of deep inspiration (DI) that may be evidenced during methacholine challenge. DESIGN AND SETTING: Prospective study in a laboratory performing pulmonary function tests of an academic hospital. PATIENTS AND INTERVENTIONS: Patients underwent multiple flow analysis of exhaled NO, allowing calculation of total maximum airway NO flux (J'awno) and NO concentration of expansible compartment (CAno), and received a cumulative methacholine dose of 2,000 microg. DI effect was assessed by continuous measurement of the resistance of respiratory system using the forced oscillation technique before and after DI. RESULTS: In a first phase involving 23 patients, a positive correlation between log values of J'awno and CAno was demonstrated with the degree of airway responsiveness (percentage of FEV(1) decrease). In a second phase involving 38 patients, only log CAno was correlated with responsiveness, and no significant relationship was demonstrated between J'awno or CAno and the effect of DI. Patients with smaller airways and/or distal airflow limitation exhibited a constrictive response to DI. CONCLUSION: Airway responsiveness is mainly associated with an increase in distal origin of NO output, and no relationship between exhaled NO and the effect of DI was evidenced.     

Quality, size, and composition of pediatric endobronchial biopsies in cystic fibrosis

BACKGROUND: Studies on airway remodeling in children with cystic fibrosis (CF) may be hampered by difficulty in obtaining evaluable endobronchial biopsy specimens because of large amounts of mucus and inflammation in the CF airway. We prospectively assessed how the quality of biopsy specimens obtained from children with CF compare with those from children with other airway diseases. METHODS: Fiberoptic bronchoscopy with endobronchial biopsy was performed in 67 CF children (age range, 0.2 to 16.8 years), 34 children with wheeze/asthma (W/A), and 64 control children with chronic respiratory symptoms. Up to three biopsy specimens were taken and stained with hematoxylin and eosin. Biopsy specimen size and structural composition were quantified using stereology. RESULTS: At least one evaluable biopsy specimen was obtained in 72% of CF children, in 79% of children with W/A, and in 72% of control subjects (difference was not significant). The use of large biopsy forceps (2.0 mm) rather than small biopsy forceps (1.0 mm) [odds ratio (OR), 5.8; 95% confidence interval (CI), 1.1 to 29.8; p = 0.037] and the number of biopsy specimens taken (odds ratio, 2.6; 95% confidence interval, 1.3 to 5.2; p = 0.006) significantly contributed to the success rate. Biopsy size and composition were similar between groups, except that CF children and those patients with W/A had a higher percentage of the biopsy specimen composed of muscle than did control subjects (median 6.2% and 9.7% vs 0.9%, respectively; p = 0.002). CONCLUSIONS: Biopsy size and quality are adequate for the study of airway remodeling in CF children as young as 2 months of age. Researchers should use large forceps when possible and take at least two biopsy specimens per patient. An increased airway smooth muscle content of the airway mucosa may contribute to the pathophysiology of CF lung disease.