Anxiety and depression in adolescents with asthma and in their parents. Is an increased basal cholinergic tone a possible further reason to explain the negative impact on asthma control?

To the Editor We read with interest the excellent article of Licari et al.  reporting that anxiety and depression are common in adolescents suffering from asthma as well as in their parents, mainly in mothers. The consequence of this relationship is that emotional disorders might negatively affect also the control of asthma.

Lung Function and Bronchial Hyperresponsiveness in Adults Born Prematurely. A Cohort Study.

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.

Quality of Life and Bronchial Hyper-Responsiveness in Subjects With Bronchiectasis: Validation of the Seattle Obstructive Lung Disease Questionnaire in Bronchiectasis.

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.

A study of two generic health-related quality of life questionnaires--Nottingham Health Profile and Short-Form 36 Health Survey--and of coping in patients with sensory hyperreactivity.

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 in rhesus monkeys (Macaca mulatta) is related to the airways response, but not immune measures, commonly associated with asthma.

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.

Perception of bronchoconstriction: a complementary disease marker in children with asthma.

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.

Behavioral inhibition is associated with airway hyperresponsiveness but not atopy in a monkey model of 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.

Psychological status in uncontrolled asthma is not related to airway hyperresponsiveness.

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.

Effects of obesity on perceptual and mechanical responses to bronchoconstriction in 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.

Experiences of problems in individuals with hypersensitivity to odours and chemicals.

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.

Long-term outcomes of acute irritant-induced asthma.

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.

Effects of stress and neuropeptides on airway responses in ovalbumin-sensitized rats.

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.

Placebo response in asthma: a robust and objective phenomenon.

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.

[The RHINASTHMA-Quality of Life Scale German Adapted Version: validation of a new disease specific quality of life scale for patients suffering from allergic rhinitis and bronchial hyperreactivity]. / Die RHINASTHMA-Lebensqualitätsskala German Adapted Version: Validierung einer neuartigen krankheitsspezifischen Lebensqualitätsskala für Patienten mit allergischer Rhinitis und bronchialer Hyperreaktivität.

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".

Do psychological distress and somatization contribute to misattribution of asthma? A Chilean study.

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.

Psychological status and quality of life in elderly patients with asthma.

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.

Effect of viewing a humorous vs. nonhumorous film on bronchial responsiveness in patients with bronchial asthma.

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.