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Rationale: Bronchopulmonary dysplasia and the long-term consequences of prematurity are underrecognized entities, unfamiliar to adult clinicians. Well described by the pediatric community, these young adults are joining the ranks of a growing population of adults with chronic lung disease., Objectives: To describe the quality of life, pulmonary lung function, bronchial hyperresponsiveness, body composition, and trends in physical activity of adults born prematurely, with or without respiratory complications., Methods: Four groups of young adults born in Canada between 1987 and 1993 were enrolled in a cohort study: (1) preterm subjects with no neonatal respiratory complications, (2) preterm subjects with neonatal respiratory distress syndrome, (3) preterm subjects with bronchopulmonary dysplasia, and (4) subjects born at term. The following measurements were compared across the four groups: health-related quality of life, respiratory health, pulmonary function, methacholine challenge test results, and sedentary behavior and physical activity level., Measurements and Main Results: Adult subjects who had bronchopulmonary dysplasia in infancy had mild airflow obstruction (FEV1, 80% predicted; FEV1/FCV ratio, 70) and gas trapping compared with others. They also had less total active energy expenditure and more time spent in sedentary behavior compared with subjects born at term. All preterm groups had a high prevalence of bronchial hyperresponsiveness compared with term subjects., Conclusions: In a population-derived, cross-sectional study, we confirmed previous reports that adults 21 or 22 years of age who were born prematurely with neonatal bronchopulmonary dysplasia are more likely to have airflow obstruction, bronchial hyperresponsiveness, and pulmonary gas trapping than subjects born prematurely without bronchopulmonary dysplasia or at term. Clinicians who care for adults need to be better informed of the long-term respiratory consequences of premature birth to assist young patients in maintaining lung function and health.

Background: Bronchiectasis can adversely affect quality of life. However, the tests examining quality of life in bronchiectasis are not sufficient. We examined the validity of a measure designed for COPD, the Seattle Obstructive Lung Disease Questionnaire (SOLQ), in bronchiectasis. In addition, we aimed to compare the quality of life of subjects with bronchiectasis and bronchial hyper-responsiveness with that of those without to identify the effective factors., Methods: We studied 78 subjects with clinically stable bronchiectasis and 41 healthy controls matched for age and sex. Subjects were assessed by the SOLQ. A detailed history, physical examination, the Medical Outcomes Study 36-Item Short Form questionnaire, the Hospital Anxiety and Depression Scale, and spirometric measurements were obtained., Results: Cronbach α coefficients, which reflected internal consistency, were >0.70 for all SOLQ components except for treatment satisfaction. SOLQ component scores correlated with all of the component scores of the Medical Outcomes Study 36-Item Short Form questionnaire and the Hospital Anxiety and Depression Scale, confirming their concurrent validity. All SOLQ scores correlated positively with percent-of-predicted FEV1, whereas the physical function, treatment satisfaction, and emotional function correlated negatively with the exacerbation frequency in Pearson analysis. Emotional and physical functions were positively associated with percent-of-predicted FEV1 in linear regression analysis. Compared with subjects without bronchial hyper-responsiveness, those with bronchial hyper-responsiveness had lower FEV1/FVC and more exacerbations/y. Compared with bronchiectasis subjects without bronchial hyper-responsiveness, those with bronchial hyper-responsiveness had significantly lower SOLQ, physical function, and coping skills scores but not emotional function and treatment satisfaction., Conclusions: The SOLQ is a valid instrument for determining quality of life in subjects with bronchiectasis. Subjects with bronchiectasis and bronchial hyper-responsiveness had a poorer quality of life, lower baseline spirometric values, and more frequent exacerbations, suggesting more severe disease., (Copyright © 2015 by Daedalus Enterprises.)

Background: Sensory hyperreactivity (SHR) is one explanation for airway symptoms induced by chemicals and scents. Little is known about health-related quality of life (HRQOL) and coping, in this group of patients. A study was done in patients with SHR to (1) compare the Nottingham Health Profile (NHP) and the Short-Form 36 Health Survey (SF-36) in regard to their suitability, validity, reliability, and acceptability; (2) evaluate how the patients cope with the illness; (3) assess whether there are differences between women and men with respect to HRQOL and coping; and (4) assess whether there are differences between patients and normative data with respect to HRQOL and coping., Methods: A total of 115 patients (91 women) with SHR were asked to answer five questionnaires: a study-specific questionnaire, the Chemical Sensitivity Scale for Sensory Hyperreactivity (CSS-SHR), the NHP, the SF-36, and the Jalowiec Coping Scale-60., Results: Eighty-three patients (72%; 70 women) completed all questionnaires. The SF-36 scores were less skewed and more homogeneously distributed and showed fewer floor and ceiling effects than the NHP scores. The SF-36 was also discriminated better between patients with high and low CSS-SHR scores. The reliability standard for both questionnaires was satisfactory. There were no gender differences in HRQOL. Patients with SHR had significantly lower HRQOL scores than the normative data in comparable domains of the NHP and the SF-36: emotional reactions/mental health, energy/vitality, physical mobility/functioning, and pain/bodily pain. In social isolation/functioning, the results were different; the NHP scores were similar to the normative data and the SF-36 scores were lower. The most commonly used coping styles were optimistic, self-reliant, and confrontational. Women used optimistic coping more than men. Compared with the normative group, patients with SHR used confrontational and optimistic coping more and emotive coping less., Conclusions: The current findings showed that both the NHP and the SF-36 were reliable instruments; but the results suggest that the SF-36 is a more sensitive instrument than the NHP for elucidating HRQOL in patients with SHR. Patients with SHR experienced a poor HRQOL and they followed the Western tradition of preferring problem-focused coping strategies to palliative and emotive strategies.

Behavioral inhibition reflects a disposition to react warily to novel situations, and has been associated with atopic diseases such as asthma. Retrospective work established the relationship between behavioral inhibition in rhesus monkeys (Macaca mulatta) and airway hyperresponsiveness, but not atopy, and the suggestion was made that behavioral inhibition might index components of asthma that are not immune-related. In the present study, we prospectively examined the relationship between behavioral inhibition and airway hyperresponsiveness, and whether hormonal and immune measures often associated with asthma were associated with behavioral inhibition and/or airway hyperresponsiveness. In a sample of 49 yearling rhesus monkeys (mean=1.25 years, n=24 behaviorally inhibited animals), we measured in vitro cytokine levels (IL-4, IL-10, IL-12, IFN-γ) in response to stimulation, as well as peripheral blood cell percentages, cortisol levels, and percentage of regulatory T-cells (CD3+CD4+CD25+FOXP3+). Airway reactivity was assessed using an inhaled methacholine challenge. Bronchoalveolar lavage was performed and the proportion of immune cells was determined. Behaviorally inhibited monkeys had airway hyperresponsiveness as indicated by the methacholine challenge (p=0.031), confirming our earlier retrospective result. Airway hyperresponsiveness was also associated with lower lymphocyte percentages in lavage fluid and marginally lower plasma cortisol concentrations. However, none of the tested measures was significantly related to both behavioral inhibition and airway hyperresponsiveness, and so could not mediate their relationship. Airway hyperresponsiveness is common to atopic and non-atopic asthma and behavioral inhibition has been related to altered autonomic activity in other studies. Our results suggest that behavioral inhibition might index an autonomically mediated reactive airway phenotype, and that a variety of stimuli (including inflammation within lung tissue that is not specifically associated with behavioral inhibition) may trigger the airways response.

Introduction: Asthma guidelines use symptoms as the most important aspect of asthma control. Symptom perception varies widely between individuals. Over-perception as well as underperception of bronchoconstriction could have a negative effect on asthma management. We hypothesized that perception of bronchoconstriction in childhood asthma is not related to common measures of disease control. For that reason, we examined the clinical determinants of the perception of bronchoconstriction and the repeatability of perception measurements., Patients and Methods: In school-age children with moderately severe atopic asthma, we measured the perception of bronchoconstriction (decrease in forced expiratory volume in 1 second (FEV(1)) during methacholine bronchoprovocation challenges. The perception of bronchoconstriction was assessed as the slope of the relation between FEV(1) and Borg score, and as the Borg score at a 20% decrease in FEV(1) from baseline during the provocation test (PS(20)). Data from subjects who had a 20% or more decrease in FEV(1) (n = 112) were used for the analysis. Fifty-four children repeated the test after 3 months. Symptoms, use of rescue medication, and peak expiratory flows were scored in diaries during the 2 weeks before testing., Results: Symptom perception was significantly better in children without (PD(20) > 1570 μg, n = 28) than in children with airway hyperresponsiveness (PD(20) ≤ 1570 μg, n = 112), slope 0.22 versus 0.13 respectively (p < .001). Borg scores correlated with PD(20) (p = .01), baseline FEV(1) (only for slope, p = .04), and use of rescue beta agonist (p = .01), but not with other aspects of asthma control. Repeatability of Borg scores was good (slope: R = 0.59, PS(20): R = 0.52)., Conclusion: Poorer symptom perception in asthmatic children correlated with hyperresponsiveness, and was associated with lower baseline FEV(1) and less use of rescue bronchodilators. This suggests that the measurement of symptom perception should be taken into account in individual management plans for children with asthma.

Objective: To determine whether indicators of behavioral inhibition and cortisol responses to stressful situations, obtained in infancy, were associated with asthma-related measures (atopy and airway hyperresponsiveness [AHR]) approximately 2 years later., Methods: Measures reflecting inhibited temperament and cortisol response after a 25-hour separation from mother and relocation to a novel room were obtained for 21 rhesus monkeys (mean age, 109 days; range, 91-122 days). Inhibited temperament was measured by reduced emotionality and increased vigilance. Atopy and AHR were assessed after 2 years (age range, 19-35 months) using skin tests to common aeroallergens and inhaled methacholine challenge, respectively., Results: No associations were found between atopy and either behavioral inhibition or cortisol levels (p > .56). Low emotionality was associated with AHR (r = 0.47, p = .03), and a trend was found for blunted cortisol responsiveness and AHR (r = 0.42, p = .06)., Conclusions: Inhibited temperament and blunted cortisol responsiveness may be related to the development of AHR that is common to both nonatopic and atopic asthma phenotypes and may indicate risk for nonatopic asthma specifically.

Background: Airway hyperresponsiveness (AHR) is the characteristic functional abnormality of asthma, and previous studies have shown the potential for AHR to be influenced by psychological factors, yet the relationship between anxiety and/or depression and AHR remains unclear in patients with asthma., Objective: To explore the relationship between psychological status and AHR in asthma patients., Methods: In a cross-sectional study, 168 adult subjects were recruited with physician-diagnosed uncontrolled asthma and a positive result for AHR in methacholine (Mch) challenge test. Psychological status, asthma control, and asthma quality of life were assessed using Zung self-rating anxiety/depression scale, asthma control test (ACT), and asthma quality of life questionnaire (AQLQ), respectively. AHR severity was evaluated and quantified by the provocative concentration of Mch, which evoked a given decrease of 20% in FEV(1)., Results: A total of 70.23% of recruited patients (n = 118) met the diagnostic criteria for anxiety and/or depression. There was a trend between negative psychological status and AHR in asthma patients that did not reach statistical significance, but no independent effects of negative mood states (anxiety, depression, or both) on AHR were established. Further, analyses revealed that only anxiety is associated with worse asthma control (p = 0.029), and a significant interaction effect of depression and anxiety accounted for lower asthma-related quality-of-life scores (p < 0.001)., Conclusions: AHR and psychological status are loosely related to each other even if in uncontrolled asthma.

Rationale: The influence of obesity on the perception of respiratory discomfort during acute bronchoconstriction in asthma is unknown., Objectives: We hypothesized that the respiratory impairment associated with an increased body mass index (BMI) would predispose to greater perceived symptom intensity during acute airway narrowing. We therefore compared relationships between induced changes in dyspnea intensity and lung function during methacholine (MCh) bronchoprovocation in obese (OBA) and normal-weight (NWA) individuals with asthma of mild to moderate severity., Methods: High-dose MCh challenge tests to a maximum 50% decrease in FEV(1) were conducted in 51 NWA (BMI, 18.5-24.9 kg/m(2); 29% male) and 45 OBA (BMI, 30.1-51.4 kg/m(2); 33% male) between 20 and 60 years of age. Serial spirometry, inspiratory capacity (IC), plethysmographic end-expiratory lung volume (EELV) and dyspnea intensity using the Borg scale were measured throughout bronchoprovocation., Measurements and Main Results: Spirometry and airway sensitivity were similar in both groups; baseline EELV was lower (P < 0.0005) and IC was higher (P = 0.007) in OBA compared with NWA. From baseline to PC(20), EELV increased more in OBA (20% predicted) than NWA (13% predicted) (P = 0.008) with concomitant greater reductions in IC (P < 0.0005). Dyspnea ratings were not different for a given FEV(1) or IC across groups. By mixed effects regression analysis, relationships between induced dyspnea and changes in lung function parameters were not influenced by BMI, sex, or their interaction., Conclusions: Perceptual responses to MCh-induced bronchoconstriction and lung hyperinflation were similar in obese and normal-weight individuals with asthma despite significant group differences in baseline lung volumes.

Rationale: The long-term outcomes of acute irritant-induced asthma (IIA) are mostly unknown., Objectives: To study the long-term outcomes of IIA., Methods: We reassessed 35 subjects who experienced IIA at a mean interval of 13.6 +/- 5.2 years., Measurements and Main Results: The causal agent was chlorine in 20 cases (57%). At diagnosis, the mean +/- SD FEV(1) was 74.5 +/- 19.5% predicted, and all subjects showed bronchial hyperresponsiveness. At reassessment, all subjects reported respiratory symptoms, and 24 (68%) were on inhaled steroids. There were no significant improvements in FEV(1) and FEV(1)/FVC values. Twenty-three subjects had a methacholine test, and only six subjects had normal levels of responsiveness. Of the remaining 12 subjects, six had improvement in FEV(1) after bronchodilator >or=10%. In samples of induced sputum obtained from 27 subjects, six had eosinophils >or=2%. Levels of inflammatory and remodeling mediators were higher than in control subjects but were no different from subjects with occupational asthma due to sensitization. Quality of life score was 4.4 +/- 1.5 on a 0 (worst) to 7 (best) scale. Twelve subjects had an abnormal depression score., Conclusions: This study provides the first evidence of significant long-term impact of acute IIA on various outcomes.

Aim: The purpose of the study was to describe how individuals with hypersensitivity to odours and chemicals handle their problems., Background: One group of patients we often encounter consists of those with upper and lower respiratory problems who also have a pronounced sensitivity to odours and chemicals. Earlier studies have shown that these symptoms can be related to sensory hyperreactivity (SHR). This hyperreactivity is characterised by respiratory tract symptoms triggered by odours and chemicals, along with high sensitivity to inhaled capsaicin and a positive score on the chemical sensitivity scale for SHR. However, there is still a lack of studies in which SHR sufferers describe their situations in their own words., Design: The study was conducted using a qualitative approach., Methods: Eight individuals with confirmed SHR were selected from a population-based epidemiological study and interviewed. A qualitative content analysis was performed on the data., Results: Four themes emerged from the data analysis: Limitations in one's life situation, Lack of understanding from others, Concern that the symptoms will develop into a serious disease and Disparagement of one's own personal experience. The results show how individuals manage their daily lives with the help of various strategies, how they relate to other people, how they cope with their concerns and the fact that they sometimes choose to disparage their own experience of their problems., Conclusion: The results indicate that people with SHR experience limitations in their life situations. These limitations consist of the adjustments they make to avoid triggering factors., Relevance to Clinical Practice: To improve care, nurses need to know how people experience SHR and how they cope with their hypersensitivity to odours and chemicals.

Background: Placebos are hypothesized to exert positive effects on medical conditions by enhancing patient expectancies. Recent reviews suggest that placebo benefits are restricted to subjective responses, like pain, but might be ineffective for objective physiologic outcomes. Nevertheless, mind-body links and placebo responsivity in asthma are widely believed to exist., Objective: We carried out a randomized, double-blind investigation to (1) determine whether placebo can suppress airway hyperreactivity in asthmatic subjects, (2) quantify the placebo effect, (3) identify predictors of the placebo response, and (4) determine whether physician interventions modify the placebo response., Methods: In a double-blind, crossover design investigation, 55 subjects with mild intermittent and persistent asthma with stable airway hyperreactivity were randomized to placebo or salmeterol before serial methacholine challenges. Subjects were additionally randomized to physician interactions that communicated either positive or neutral expectancies regarding drug effect., Results: Placebo bronchodilator administration significantly reduced bronchial hyperreactivity compared with baseline (the calculated concentration of methacholine required to induce a 20% decrease in FEV(1) nearly doubled); 18% of subjects were placebo responders by using conservative definitions. Experimental manipulation of physician behavior altered perceptions of the physician but not the magnitude or frequency of the placebo response., Conclusions: Objective placebo effects exist in asthma. These responses are of significant magnitude and likely to be meaningful clinically. The placebo response was not modulated by alterations in physician behavior in this study., Clinical Implications: The placebo response in patients with asthma is important in understanding the limitations of clinical research studies and in maximizing safe and effective therapies. This article confirms the existence of a strong placebo response in an objective and clinically relevant measure of disease activity.

Background: In 2003 Baiardini et al. presented the RHINASTHMA questionnaire, which measures the impairment of quality of life in patients with rhinitis and asthma and takes the "united airway disease" model into its account. The aim of our study was to create a valid version of this questionnaire adapted for use with German-speaking subjects., Methods: Datasets recorded for 85 patients were analysed for sensitivity, reliability and validity of the new questionnaire. For this purpose, as well as the symptom scores, disease-specific and generic quality of life questionnaires were also used as a measure of validity., Results: A correlation analysis and Cronbach's alpha indicated that the RHINASTHMA scale is satisfactory from the aspect of reliability. Good validity was also shown in terms of discrimination and agreement for all items and scores. In addition, all the observed parameters reacted sensitively to clinical improvements of the health status., Conclusion: The RHINASTHMA questionnaire makes it possible to determine how badly the quality of life is impaired by rhinitis and asthma, based on the paradigm of "united airway disease".

Objective: The aim of this study was to assess the association between asthma and distress by whether symptoms of asthma present alone or are accompanied by atopy or bronchial reactivity to methacholine [bronchial responsiveness (BHR)], hence, to ascertain whether overreporting of asthma symptoms occurs in those with distress., Methods: We studied 601 young adults in four groups: those with asthma symptoms and atopy or positive BHR, those with asthma symptoms only, those with atopy or positive BHR only, and controls. The main independent variables were the General Health Questionnaire-12 (GHQ-12) and 45 physical symptoms to assess somatization., Results: The somatization score was highly associated with asthma symptoms alone and asthma symptoms with BHR or atopy, GHQ-12 with asthma alone and asthma and BHR or atopy related to a control group. After adjustment for somatization, GHQ-12 was not associated with the asthma outcomes., Conclusions: Excess asthma symptom reporting due to psychological distress or somatization as a cause of the association is unlikely.

Objective: The aim of this study was to investigate the influence of stress and neuropeptides on airway responses in ovalbumin (OVA)-sensitized rats., Methods: Three experimental conditions were employed: neonatal capsaicin treatment, foot shock stress and OVA sensitization. For neuropeptide depletion, male Wistar rats were neonatally treated with capsaicin (50 mg/kg) or with control solution 2 days after birth. Ninety days later, they were injected with OVA and aluminum hydroxide (ED0) or no injection. Thereafter, rats of the stressed groups were individually placed in a shuttle box where they received 50 mild escapable foot shocks/day; the stressful stimuli were repeated until ED14, when the animals received OVA aerosol. Pulmonary mechanic function was measured before and after OVA challenge in anesthetized and mechanically ventilated rats., Results: Data on ultrasonic vocalizations and corticosterone showed high levels of anxiety in stressed animals. As expected, a significant increment in airway elastance and resistance after the OVA challenge was found in sensitized rats compared to non-sensitized ones. Capsaicin treatment decreased the values of elastance in sensitized and non-stressed rats; however, after the OVA challenge, elastance was increased in stressed animals. No differences were found in the levels of resistance among sensitized and non-stressed rats; however, a reduced increment in resistance was verified in capsaicin-treated, stressed animals., Conclusions: Our results suggest that neurokinin depletion and stress may affect smooth muscle tonus around the airways during an anaphylactic reaction. These data suggest that stress and neuropeptides play a significant role in pulmonary function in OVA-sensitized rats., (Copyright (c) 2007 S. Karger AG, Basel.)

The psychological status and quality of life of 70 stable patients with asthma age > or =60 years and 40 age-matched comparison subjects were examined. The patients with long-standing asthma (duration > or = 8 years) had lower quality-of-life scores than those with recent-onset asthma (duration < 8 years). In multivariate linear regression analysis with adjustment for age, gender duration of disease, and level of bronchial hyperreactivity, worse quality of life was predicted by anxiety, depression, and asthma severity scores. In elderly patients with long-standing asthma, disease severity significantly impairs quality of life. Impaired quality of life in these patients may be partly related to psychological status indicators.

The effect of viewing a humorous film on bronchial responsiveness to methacholine [methacholine study: 20 healthy participants and 20 patients with house dust mite (HDM)-allergic bronchial asthma (BA)] or to epigallocatechin gallate (EGCg; EGCg study: 15 normal participants and 15 EGCg-allergic BA patients) was studied. At baseline, bronchial challenge test to methacholine (20 normal participants and 20 HDM-allergic BA patients) or EGCg (15 normal participants and 15 EGCg-allergic BA patients) were performed. After 2 weeks, patients and healthy participants were randomly assigned to watch a humorous or a nonhumorous film. Two weeks later, the alternate film was watched. Immediately after viewing, bronchial challenge test to methacholine or ECGg to each study group were performed. Viewing a humorous film significantly reduced bronchial responsiveness to methacholine or EGCg, while viewing a nonhumorous film failed to do so in BA patients without affecting bronchial responsiveness to methacholine or EGCg in healthy participants. These findings indicate that viewing a humorous film may be useful in the treatment and study of BA.

The effects of short treatments (7 days) with paroxetine and with reboxetine on the reactivity to inhalations of 35% carbon dioxide (CO2)/65% oxygen (O2) were compared in 28 patients with Panic Disorder who had positive responses to 35% CO2 inhalations. A double-blind, randomized design was applied. Each patient was given the 35% CO2 challenge on days 0 (before starting the treatment) and 7. Anxiety reactivity to CO2 decreased significantly with both drugs but the decrease was significantly stronger in the group treated with paroxetine. The rate of patients whose reactivity has reduced of at least 50% after 7 days was significantly higher in the group treated with paroxetine (10/14, 71.5%) than in the one treated with reboxetine (3/14, 21.5%). These results indicate that the modulation of the serotonergic system is more relevant for CO2 hyperreactivity than the modulation of the noradrenergic one.

Aim: To evaluate quality of life (QOL) in Indian children with bronchial asthma., Methods: A disease-specific, locally appropriate QOL questionnaire was administered in asthmatic children and compared with FEV1, FVC, PEFR and asthma symptom score, on three occasions., Results: QOL score had strong negative correlation with symptom score and weaker positive correlation with pulmonary function tests., Conclusion: Disease-specific QOL score correlates inversely with symptom score in children with bronchial asthma.

Little is known about the management of asthma in adolescents. We aimed at evaluating these aspects, through a specific questionnaire, in the real life of adolescents with allergic asthma. The questionnaire was administered to a group of adolescents after a diagnosis of allergic asthma. The diagnosis was based on history, clinical examination, pulmonary function tests and allergy tests. One hundred and fifteen adolescents (65 males, mean age 16.5 years) fulfilled the criteria for allergic asthma. The questionnaire explored demography, family history, clinical history, previous diagnosis, therapy, attitude towards therapy and social aspects. The mean actual FEV1 was 87 +/- 10%. Methacholine challenge was carried out in 79 patients and was always positive (PD20 < 1,200 microg), whereas 36 patients underwent reversibility test. According to GINA guidelines, severity of asthma resulted intermittent in 62, mild persistent in 31, moderate in 19 and severe in three patients. In 61% of cases teachers were not aware of the disease. Asthma was managed by general practitioners, allergists and pulmonologists, but PFT/allergy tests had never been performed in 14% of patients. Forty-two per cent of the adolescents received no therapy at all, and only 15% of those with persistent asthma were receiving a stable treatment. Seventy-four per cent of adolescents preferred the inhaled, as against the oral, route. From a clinical and functional point of view, asthma in adolescents did not differ from other age ranges. Nevertheless, the management (diagnosis and therapy) emerged to be unsatisfactory from many points of view.

Some asthma patients and physicians who treat asthma have reported that stress worsens their disease. It has also recently been shown that chronic stressful life events increase airway inflammation 6-24 h after inhalation of antigen in patients with allergic asthma. However, there is no data regarding the effect of an acute stressor on the airway constriction that occurs within minutes of antigen inhalation (early pulmonary response) in this same population. The aim of this study was to examine this effect in eight females with allergic asthma. Each subject was challenged with increasing concentrations of inhaled allergen on a control visit (no stress) and on a stress visit, when they were asked to verbally recount an emotionally stressful situation between each concentration. Systolic (SP) and diastolic (DP) blood pressure, cardiac frequency (fC) and forced expiratory volume in one second (FEV1) were measured on both visits. SP, DP and fC were statistically increased on the stress visit as compared to control. Per cent decrease in FEV1 at the same last dose of allergen was significantly less on the stress visit (11.2 +/- 7.0%) compared to control (15.0 +/- 8.7%). These findings suggest that the early pulmonary response to inhaled allergen is attenuated while verbally re-experiencing an acute emotional stressor in females with allergic asthma.

Objective: Despite the long-standing clinical assumption that stress and asthma morbidity are associated, convincing experimental evidence on mechanisms has been unavailable. A wide range of immunological, endocrinological, and neuronal pathways are known to mediate and modulate a systemic stress response. Interestingly, most of these mediators play a crucial role in initiating and perpetuating symptoms associated with bronchial asthma. To explore potential mechanisms linking stress to asthma exacerbation we developed an animal model that combines allergic airway inflammation and exposure to stress., Methods: CBA/J mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and challenged with OVA aerosol via the airways. Additionally, some mice were stressed by exposure to an ultrasonic stressor. Airway hyperreactivity (AHR) was measured in vitro by electric field stimulation (EFS) of tracheal smooth muscle elements. Bronchoalveolar lavage fluid (BAL) was obtained and cell numbers determined. Cytokine levels of IL-4, IL-5, and IFN-gamma in BAL were determined by ELISA., Results: Our findings demonstrate that exogenously applied stress dramatically enhances airway reactivity in OVA-sensitized and challenged mice. Further, stress significantly increases allergen-induced airway inflammation identified by increased leukocyte (ie, eosinophil) numbers in bronchoalveolar lavage fluids., Conclusions: We found further evidence that stress can indeed exacerbate airway hyperreactivity and airway inflammation in an animal model of allergic bronchial asthma and now introduce a novel murine model to identify stress-triggered pathways, including mediators as neurohormones, neuropeptides, and markers of inflammation.

Carbon dioxide (CO2) inhalation induces acute anxiety and panic attacks in patients with Panic Disorder (PD). Anti-panic drugs decrease CO2 reactivity after the first days of treatment; however, the clinical meaning of this finding has not yet been established. This study investigated the effects of treatment with tricyclic antidepressants and selective serotonin re-uptake inhibitors (SSRIs) on CO2 reactivity and compared the relationships between 35% CO2 hyperreactivity modulation and short-term clinical outcome. One hundred twenty-three patients with PD with or without agoraphobia who were hyperreactive to CO2 were randomly assigned to treatment groups with imipramine, clomipramine, paroxetine, sertraline, or fluvoxamine. A double-blind, randomized design was applied. Each patient received the 35% CO2 challenge on days 0, 7, and 30. The severity of clinical symptomatology was measured on days 0 and 30. Decreased hyperreactivity to 35% CO2 in all five treatment groups was already evident after the first week. The decrease in CO2 reactivity at the end of treatment was proportional to the degree of clinical improvement. Multiple regression analyses showed that the decrease in CO2 reactivity after the first week was a significant predictor for good clinical outcome after one month. The results of this study confirm evidence that psychoactive drugs effective in the treatment of PD decrease CO2 hyperreactivity. They also suggest that precocious modulation of CO2 reactivity might fairly reliably predict short-term clinical outcome in patients with "respiratory" PD.

Symptoms of atopic asthma often disappear around puberty. The authors recently demonstrated that this clinical remission is accompanied with ongoing airways inflammation in most subjects. The discrepancy between lack of symptoms and persistent airway inflammation suggests that perception of the symptoms is unclear. In the present study, young adults in clinical remission of atopic asthma assigned themselves a modified Borg score during methacholine and adenosine-5'-monophosphate induced bronchoconstriction. Borg scores of subjects in clinical remission were compared with those of symptomatic asthmatic subjects. A marked variation in the Borg scores at a 20% fall in the forced expiratory volume in one second was found. Significant differences in Borg scores between remission patients and asthmatics could not be detected. It was concluded that perception of dyspnoea, induced with methacholine and adenosine challenge, is similar in young adults in clinical remission of atopic asthma compared to that of patients with symptomatic asthma. Hence, an unclear perception seems to be an unlikely explanation for the discrepancy between lack of symptoms and ongoing inflammation. Other factors, including both physical and psychological ones, may play a role in the apparent absence of symptoms, thereby potentially leading to undertreatment.

Background: A study was undertaken to investigate quality of life in asthma, defined by differing criteria, to see which may be most appropriate in epidemiological studies., Methods: The 426 adults were participants in the follow up phase of the European Community Respiratory Health Survey (ECRHS) in Melbourne. As part of the laboratory visit, participants completed the SF-36 quality of life questionnaire, a detailed respiratory questionnaire, and underwent lung function testing., Results: Both the physical component summary and the mental component summary scores were significantly worse in those with wheeze in the previous 12 months than in those without wheeze. Only the mental component summary score was significantly worse in those with current asthma than in those without. In contrast, in those with current asthma or bronchial hyperreactivity only, neither of the summary scales was significantly different between cases and controls., Conclusions: Quality of life is severely impaired in individuals with wheeze in the previous 12 months while individuals with current asthma or bronchial hyperreactivity alone did not appear to have significantly reduced quality of life.

The perception of bronchoconstriction may be modulated by airway inflammation. However, the effect of inhaled corticosteroid (ICS) treatment on perception in subjects with asthma has received limited study. The aim of this study was to determine the effect of inhaled budesonide on the perception of breathlessness induced by histamine challenge. Thirty-five subjects with poorly controlled asthma were randomized to receive budesonide (1,600 or 3,200 microg/d) for 8 wk, followed by 8 wk at 1,600 microg/d and subsequent downtitration according to a clinical algorithm. Borg scores were recorded during histamine challenges performed at baseline and at 8, 16, 24, 48, and 72 wk. Perception was estimated as the slope of Borg/% fall FEV(1). The Borg/FEV(1) slope increased significantly after 8 wk of budesonide (0.09 [0.08-0.12] to 0.15 [0.11-0.19], p = 0.002), and remained increased compared with baseline values at all subsequent visits. There were no significant differences in Borg/ FEV(1) slope between subjects who were and were not taking ICS at study entry. The magnitude of change in the Borg/FEV(1) slope did not differ significantly between treatment groups and was not related to changes in baseline FEV(1), airway hyperresponsiveness, blood eosinophils, or serum eosinophil cationic protein (ECP). We conclude that treatment with budesonide enhances the perception of airway narrowing, but the effect is unrelated to budesonide dose, or to changes in circulating eosinophil markers.

In a two-stage detection program, subjects with signs of obstructive airway disease were selected from a random sample of the general population. Subjects (n = 82) were randomly assigned to either fluticasone propionate 250 microg twice a day or placebo twice a day via pMDI in a 1-yr, double-blind trial if they met criteria for persistent airway obstruction, increased bronchial hyperresponsiveness, or a rapid decline in FEV(1). Main outcome measures were postbronchodilator FEV(1), quality-adjusted life years (QALYs), and direct medical cost. Secondary measures were prebronchodilator FEV(1), PC(20), health-related quality of life (CRQ), symptom-free weeks, episode-free weeks, exacerbations, and indirect cost. Subgroup analysis was based on reversibility of obstruction. Analysis revealed a significant gain in postbronchodilator FEV(1) (98 ml/yr; p = 0.01) in favor of fluticasone. Only subjects with reversible obstruction showed an improvement in PC(20) (1.4 doubling dose; p = 0.03). Early treatment resulted in 2.7 QALYs gained per 100 treated subjects (p = 0.17) and in a clinically relevant improvement in dyspnea (CRQ; p < 0.03). The incremental cost effectiveness ratios were US$13,016/QALY for early treatment and US$33,921/QALY for the combination of detection and treatment. The incremental cost for one additional subject with a clinically relevant difference in dyspnea was US$1,674. In conclusion, early intervention with fluticasone resulted in significant health gains at relatively low financial cost.

The inter-relationship between the perception of bronchoconstriction, bronchial hyper-responsiveness and temporal adaptation in asthma is still a matter of debate. In a total of 52 stable asthmatic patients, 32 without airway obstruction ¿forced expiratory volume in 1 s (FEV(1))/vital capacity (VC) 84.1% (S.D. 7.9%), and 20 with airway obstruction [FEV(1)/VC 60% (4%)], we assessed the perception of bronchoconstriction during methacholine inhalation by using: (i) the slope and intercept of the Borg and VAS (Visual Analog Scale) scores against the decrease in FEV(1), expressed as a percentage of the predicted value; and (ii) the Borg and VAS scores at a 20% decrease in FEV(1) from the lowest post-saline level (PB(20)). Bronchial hyper-responsiveness was assessed as the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)FEV(1)). The reduction in FEV(1) was significantly related to the Borg and VAS scores, with values for the group mean slope and intercept of this relationship of 0.13 (S.D. 0.08) and -1.1 (3.02) for Borg, and 1.5 (1.19) and -12.01 (35) for VAS. PB(20) was 3 (1.75) with Borg scores and 34.6 (20.5) with VAS scores. Compared with the subgroup without airway obstruction, the obstructed subgroup exhibited similar slopes, but lower Borg and VAS intercepts. For similar decreases in FEV(1) (5-20% decreases from the lowest post-saline values), the Borg and VAS scores were lower in the non-obstructed than in the obstructed subgroup. PC(20)FEV(1) was significantly related to both Borg PB(20) and VAS PB(20) when considering all patients. When assessing the subgroups, PC(20)FEV(1) was related to Borg PB(20) and VAS PB(20) in the non-obstructed subjects, but not in the obstructed subjects. In neither subgroup was the log of the cumulative dose related to the Borg and VAS scores at the end of the test. We conclude that, unlike in previous studies, the ability to perceive acute bronchoconstriction may be reduced as background airflow obstruction increases in asthma. Bronchial hyper-responsiveness did not play a major role in perceived breathlessness in patients without airway obstruction, and even less of a role in patients with obstruction. The cumulative dose of agonist did not appear to influence the perception of bronchoconstriction.

Objective: Smokers who develop chronic airflow limitation (CAL) do not usually present for medical attention until their lung disease is well advanced. In contrast, asthmatic subjects experience acute symptoms and present for care early in the course of their disease. The aim of this study was to determine whether subjects with asthma differ from smokers with CAL in their ability to perceive acute methacholine-induced bronchoconstriction., Methodology: Thirteen subjects with diagnosed asthma and 10 current smokers with CAL, defined as forced expiratory volume in 1 s (FEV1) < 75% predicted and FEV1/forced vital capacity < 80%, with no previous diagnosis of asthma, were challenged with methacholine. Symptom severity was recorded on a Borg scale. Lung volumes were measured before challenge and after the FEV1 had fallen by 20%., Results: After methacholine falls in FEV1 were similar in the asthmatic subjects and smokers. The regression lines relating change in FEV1 to symptom score were significantly steeper in asthmatic subjects than smokers (0.13 +/- 0.04, 0.03 +/- 0.04, respectively, P < 0.01). At 20% fall in FEV1 there were no significant differences between asthmatic subjects and smokers in the magnitude of change of lung volumes., Conclusions: In asthmatic subjects, symptoms are closely related to change in FEV1. In smokers with CAL, symptoms change little during bronchial challenge despite large changes in FEV1. The differences in perception between the two subject groups are not due to differences in acute hyperinflation during challenge. We propose that heavy smokers may adapt to poor lung function, or may have damaged sensory nerves as a result of prolonged cigarette smoking.

Background: Family studies suggest that asthma has an increased familial occurrence, but the hypothesis of a genetic predisposition to IgE response and bronchial hyperresponsiveness (BHR) on the expression of nonatopic asthma is controversial., Objective: The aim of this study was to evaluate familial predisposition to IgE response and BHR on expression of nonatopic asthma., Methods: One hundred four parents of nonatopic asthmatic children, 154 parents of atopic asthmatic children, 78 parents of atopic nonasthmatic control children, and 80 parents of nonatopic control children provided questionnaire data and underwent allergy skin prick tests with 10 inhalant allergens and methacholine bronchial provocation tests. Total serum IgE levels were determined in 352 parents (134 with atopic asthmatic children, 87 with nonatopic asthmatic children, 65 with atopic control children, and 66 with nonatopic control children)., Results: Prevalence of asthma, based on questionnaire data and on BHR to methacholine, was higher among parents of nonatopic asthmatic children (10.6%) and atopic asthmatic children (9.1%) than among those of nonatopic control children (1.3%). BHR to methacholine was higher among parents of nonatopic asthmatic children (19.2%) and atopic asthmatic children (16.2%) than among those of atopic and nonatopic control children (5.1% and 1.3%, respectively). The percentage of positive skin test responses to 10 inhalant allergens was higher among parents of atopic asthmatic children (43.9%), nonatopic asthmatic children (39.4%), and atopic control children (38.5%) than among those of nonatopic control children (23.7%). Geometric means (IU/mL +/- SEM) of total serum IgE were higher among parents of atopic and nonatopic control children than among those of nonatopic control children (2.11 +/- 0.05 vs 2. 20 +/- 0.06 vs 2.09 +/- 0.07 vs 1.92 +/- 0.06)., Conclusion: Nonatopic asthma runs in families. The prevalence of positive skin test responses to inhalant allergens, BHR to methacholine, and total serum IgE levels is higher among the parents of nonatopic and atopic asthmatic children than among those of nonatopic control children.

The aim of this study was to investigate a possible interrelation between bronchial hyperreactivity and psychological hyperreactivity. In order to record changes in both bronchial and psychological reactions throughout the menstrual cycle, 10 women out-patients with moderate asthma were followed up for six months, and their physical and psychological status as well as their reactions to life-events and environmental influences were assessed through self-reporting measures and weekly psychotherapeutic sessions. Psychotherapy was used both as a supplement to the medical treatment and as a method of data collection. A relationship between lowered resistance to stress, lowered resistance to infections and increased bronchial hyperreactivity is suggested as background aetiological factors for the exacerbation of asthma around menstruation.

In epidemiological studies, defining asthma as the presence of airway hyperresponsiveness (AHR) plus recent symptoms leaves two groups of subjects whose clinical significance is unclear: those with asymptomatic AHR, and those with symptoms only. The aim of the study was to determine whether subjects with symptoms only differ from the normal and asthmatic groups in the perception of airway obstruction. Six hundred and ninety seven adults completed a questionnaire of symptoms and underwent bronchial challenge with histamine to induce airway obstruction. Recent symptoms included wheeze and morning chest tightness in the last 12 months. AHR was defined as a provoking dose of histamine causing > or = 20% fall in forced expiratory volume in one second (PD20FEV1) <3.9 micromol. At the end of the challenge test, subjects who felt wheezy or tight in the chest marked a value from 0 to 10 on a modified Borg scale, to describe the severity of the sensation. Subjects with asymptomatic AHR did not differ significantly from subjects with AHR plus recent symptoms (current asthma) either in the mean fall in FEV1 or in the median Borg score. In subjects with symptoms only, the mean Borg score was not significantly different from that of the asthmatic subjects, although mean fall in FEV1 differed significantly (p<0.0001). In subjects with symptoms only, chest tightness correlated significantly with the fall in forced vital capacity (FVC) (p= 0.011), but not with the fall in FEV1. Subjects with asymptomatic airways hyperresponsiveness were not poor perceivers of airway narrowing, but may underreport their symptoms. Subjects with symptoms only may have enhanced perception of small changes in lung function, particularly in forced vital capacity.

The objective of this study was to compare psychosocial characteristics of children with asthma and children with bronchial hyperreactivity with those of normal children. A population-based study of 2634 children (mean age, 10 years) was carried out. Pulmonary function tests of children were performed in children before and after cold air hyperventilation challenge to determine bronchial hyperreactivity. Parental assessment of children's behavior was evaluated with 15 questions about school/learning habits, level of activity, communication/affection, and sleeping patterns. A factor analysis was performed and the factor loading adjusted for confounders compared in the different groups. Asthmatic children sleep less well than normal and hyperreactive children (p < 0.001). Unexpectedly, however, all other single items did not differ significantly. As a result of the factorial analysis we obtained two factors. On the first factor, measuring school behavior and learning, there was a small difference between asthmatic and normal children, which could not be found on the second factor indicating activity and communication. We conclude that psychosocial differences of asthmatic children are less remarkable than expected. As a result of the examination of the hyperreactive children it is likely that asthmatic children are influenced more by secondary psychosocial factors than by any primary effect of asthmatic disease.

We review recently published literature on behavioral aspects of asthma, including program descriptions, reviews, and original research reports. Most of the literature on behavioral aspects of asthma has been in the area of self-management, including education, medication use, and peak flow monitoring. Recent studies of these factors have shown promising trends in reducing morbidity and in improving health care utilization outcomes. Medication adherence continues to be problematic, and its complexity is increased when comparing inhaled with oral medications and bronchodilators with anti-inflammatory agents. Psychobiologic factors that have been recently studied include perceptions of airway changes and the role of emotional responses in asthma self-management. Because the behavioral aspects of asthma play such a significant role in asthma treatment, further study is needed to determine how changes in patient behavior can improve patient quality of life.

Asthma is affected by increasing mortality and morbidity as well as by increasing costs due to hospitalizations and visits to the emergency room. It is mandatory to propose an accurate follow-up of asthmatic subjects so that they can live a normal life and avoid hospitalizations. Two tools can be used: 1) notification in a diary of daily symptoms; 2) serial assessment of peak expiratory flow rates and FEV1. These methods are widely suggested and interesting. However, several aspects including the compliance of asthmatic subjects with the assessment, remained to be examined. According to cross-sectional studies, serial measurement of non-allergic bronchial responsiveness is significantly related to the clinical and functional severity of asthma. Nevertheless, longitudinal studies do not show a satisfactory correlation. The reason for these discrepancies is unknown. Although other studies are needed to obtain direct information on the severity of bronchial inflammation, the current state of knowledge does not suggest that serial assessment of bronchial responsiveness is sufficiently valid to introduce its routine use in the follow-up of asthmatic subjects.

In assessing the effectiveness of management strategies for patients with asthma, it is important to measure outcomes which are relevant to the concerns of patients. Quality of life is one such outcome which may not be adequately reflected in lung function measurements. We have developed an asthma quality of life questionnaire (the AQLQ) for this purpose. The aim of this study was to test the validity and responsiveness of the AQLQ as a measure of change. Forty four adults with asthma were assessed on two occasions 4 months apart. On each occasion subjects completed the AQLQ and the Sickness Impact Profile (SIP). Lung function and the degree of bronchial hyperresponsiveness (BHR) were measured and diary cards were used to derive a symptom score and mean daily peak flow variability. The relation of change in AQLQ scores to change in the other outcomes was assessed. Questionnaire responsiveness was assessed by comparing the change in AQLQ scores between 19 improved and 20 stable subjects. Improvement was assessed on lung function and BHR criteria. As expected, change in AQLQ score was correlated with change in symptom score (r = 0.37, 95% CI -0.04 to 0.64) and change in BHR (r = 0.38, 95% CI 0.06 to 0.64). The associations with change in peak flow variability (r = 0.12, 95% CI -0.26 to 0.47) and change in SIP score (r = 0.18, 95% CI -0.12 to 0.45) were in the expected direction but weaker than expected. The AQLQ was capable of detecting differences between improved and stable subjects (p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

This study describes the Quebec system of compensation for occupational asthma, assessing the functional and social outcome of claimants and estimating the efficiency and cost. Information was obtained on the clinical, functional and social outcome as well as the estimated costs for 134/211 subjects (participation rate of 64%), who received compensation between 1986 and 1988. At the time of assessment (2 years and more after the diagnosis), 93% of participants still demonstrated significant bronchial hyperresponsiveness and 84% required anti-asthma medication. None of the participants remained exposed to the offending agent: 67% were working for the same or another employer, 16% were retired, 8% were retraining for a new job and 8% were still unemployed. Quality of life was mildly affected, more so than for a control group of subjects. The mean interval between the time claims were addressed and the first medicolegal decision was 8.1 months. The mean total cost (including temporary and permanent disability indemnities, medical and technical costs) was $CAN 49,200 (minimum and maximum values of $2,100 and $330,900). We conclude that for subjects with occupational asthma in Quebec: 1) the mean interval for a medicolegal decision to be made is eight months: 2) a minority is still unemployed two to four years after being assessed; 3) the quality of life is more affected than in a control group; 4) the mean cost is close to $CAN 50,000.

For measuring the interoception of airway resistance, bronchial obstructions are often simulated by flow-resistive loads applied externally (i.e. outside the body) into the respiratory flow. However, it is open to doubt whether interoception characteristics obtained in this manner are really related to the clinical pattern of complaints of asthmatic patients. Possibly such externally applied resistance simulates merely an aspect of the physics of apnoea but not a clinical and hence also psychological aspect of the same. To estimate the significance of these aspects for the perception of obstructions, this ability was measured in 25 asthmatic patients first by means of external added loads; this test was then repeated by noting the subjective assessment of bronchial obstructions caused during a routine histamine provocation test. Both interoception parameters correlated only slightly (rxy = 0.31) which is discussed as a pointer to the assumption that, among other parameters, psychological factors may considerably modify the perception of flow resistivity. No correlations were seen between the characteristic interoception value obtained by means of mesh resistivities and the different variables of the clinical pattern of symptoms. On the other hand, the interoception parameter measured on the basis of bronchial obstructions revealed significant connections with several clinical variables: the greatly increased incidence of respiratory distress at night or during certain external conditions, coping medication, physical exercise and style. It is concluded that only such parameters of perception of obstructions are clinically relevant for patients suffering from asthma, which consider not only the somaticophysical but also the psychic component of asthmatic respiratory distress.