Hyperventilation Of Cold Dry Air Research Articles

Airway obstruction and bronchial reactivity from age 1 month until 13 years in children with asthma: A prospective birth cohort study.

BackgroundStudies have shown that airway obstruction and increased bronchial reactivity are present in early life in children developing asthma, which challenges the dogma that airway inflammation leads to low lung function. Further studies are needed to explore whether low lung function and bronchial hyperreactivity are inherent traits increasing the risk of developing airway inflammation and asthmatic symptoms in order to establish timely primary preventive initiatives.Methods and findingsWe investigated 367 (89%) of the 411 children from the at-risk Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) birth cohort born to mothers with asthma, who were assessed by spirometry and bronchial reactivity to methacholine from age 1 month, plethysmography and bronchial reversibility from age 3 years, cold dry air hyperventilation from age 4 years, and exercise challenge at age 7 years. The COPSAC pediatricians diagnosed and treated asthma based on symptom load, response to inhaled corticosteroid, and relapse after treatment withdrawal according to a standardized algorithm. Repeated measures mixed models were applied to analyze lung function trajectories in children with asthma ever or never at age 1 month to 13 years. The number of children ever versus never developing asthma in their first 13 years of life was 97 (27%) versus 270 (73%), respectively. Median age at diagnosis was 2.0 years (IQR 1.2–5.7), and median remission age was 6.2 years (IQR 4.2–7.8). Children with versus without asthma had reduced lung function (z-score difference, forced expiratory volume, −0.31 [95% CI −0.47; −0.15], p < 0.001), increased airway resistance (z-score difference, specific airway resistance, +0.40 [95% CI +0.24; +0.56], p < 0.001), increased bronchial reversibility (difference in change in forced expiratory volume in the first second [ΔFEV1], +3% [95% CI +2%; +4%], p < 0.001), increased reactivity to methacholine (z-score difference for provocative dose, −0.40 [95% CI −0.58; −0.22], p < 0.001), decreased forced expiratory volume at cold dry air challenge (ΔFEV1, −4% [95% CI −7%; −1%], p < 0.01), and decreased forced expiratory volume after exercise (ΔFEV1, −4% [95% CI −7%; −1%], p = 0.02). Both airway obstruction and bronchial hyperreactivity were present before symptom debut, independent of disease duration, and did not improve with symptom remission. The generalizability of these findings may be limited by the high-risk nature of the cohort (all mothers had a diagnosis of asthma), the modest study size, and limited ethnic variation.ConclusionsChildren with asthma at some point at age 1 month to 13 years had airway obstruction and bronchial hyperreactivity before symptom debut, which did not worsen with increased asthma symptom duration or attenuate with remission. This suggests that airway obstruction and bronchial hyperreactivity are stable traits of childhood asthma since neonatal life, implying that symptomatic disease may in part be a consequence of these traits but not their cause.

Fraction of Exhaled Nitric Oxide and Bronchial Responsiveness Are Associated and Continuous Traits in Young Children Independent of Asthma

Elevated fraction of exhaled nitric oxide (FENO) and bronchial hyperresponsiveness are used as surrogate markers of asthma. These traits may be continuous in the population. The objective of this study was to investigate whether FENO and bronchial responsiveness are associated in both children with and children without a history of asthma symptoms. One hundred ninety-six 6-year-old children with no asthma symptoms, intermittent asthma symptoms, and persistent asthma were randomly included from the Copenhagen Prospective Study on Asthma in Childhood prospective clinical birth cohort of mothers with asthma. Bronchial responsiveness was assessed as the relative change in specific airway resistance after cold dry air hyperventilation. FENO measurements were performed prior to the hyperventilation test. The association between FENO and bronchial responsiveness was assessed by generalized linear models. Bronchial responsiveness and FENO exhibited a significant and linear association in the population. A doubling of FENO corresponded to an 8.4% (95% CI, 3.7%-13.1%; P = .0006) increase in airway resistance after challenge testing and remained significant after adjustment for sex, allergic rhinitis, current asthma, inhaled corticosteroid treatment, and upper respiratory tract infections prior to testing. Stratified analyses showed similar associations in children with and without asthma. FENO and bronchial responsiveness are associated and continuous traits in young children regardless of asthma symptoms, suggesting a continuous subclinical to clinical process underlying asthma. The findings also suggest caution against the use of these surrogate markers for a dichotomized approach to asthma diagnosis.

Lung function and bronchial responsiveness after Mycoplasma pneumoniae infection in early childhood

Mycoplasma (M.) pneumoniae has been associated with exacerbation of symptoms in asthmatic school children and adults; and an etiological role in asthma has been suggested. The purpose of this study was to investigate whether infection with M. pneumoniae in early childhood has a long-term influence on lung function and bronchial responsiveness. In a retrospective, clinical cohort-study children younger than 5 years-of-age when PCR-tested for M. pneumoniae were enrolled. Sixty-five children with clinical symptoms suggesting infection with M. pneumoniae during an epidemic season completed a clinical follow-up examination including lung function testing (28 PCR-positive and 37 PCR-negative). In addition to the PCR-test for M. pneumoniae all respiratory tract specimens were additionally tested for other atypical bacteria and for viruses by PCR. Lung function was measured as specific airway resistance by whole-body plethysmography and bronchial hyperresponsiveness was assessed by cold, dry air hyperventilation. Neither baseline lung function nor bronchial response to cold dry air hyperventilation differed between M. pneumoniae-positive and -negative children: mean baseline lung function were 1.17 versus 1.21 (kPa sec), P = 0.45; and mean change in specific resistance was 13% versus 9%, P = 0.42. In conclusion, M. pneumoniae infection in early childhood was not associated with long-term effects on lung function and bronchial hyperresponsiveness 2 years after infection.

A 10‐year follow‐up study of pulmonary function in symptomatic elite cross‐country skiers – athletes and bronchial dysfunctions

A high prevalence of asthma-like symptoms and abnormal bronchial reactivity to various stimuli has been reported among endurance athletes. This report presents the cases of three cross-country skiers who have shown a progressive development of airway obstruction during their sport careers. The observed decline in FEV1, FEV1/FVC and/or FVC (FEV, forced expiratory volume; FVC, forced expiratory vital capacity) was greater than expected from longitudinal regression equations describing the ageing effect on pulmonary function. The three subjects encountered abnormal respiratory discomfort during their sport activity which was not systematically associated with abnormal bronchial reactivity (either to methacholine or exercise hyperventilation). At the end of the follow-up periods (9-12 years), all three skiers presented objective signs of airflow limitations during intense exercise. This report suggests that repeated chronic hyperventilation of cold dry air in cross-country skiers for several years can induce permanent bronchial disorders which may include remodeling processes and induce ventilatory limitations during intense exercise.

Laser acupuncture in children and adolescents with exercise induced asthma

Background: Laser acupuncture, a painless technique, is a widely used alternative treatment method for childhood asthma, although its efficacy has not been proved in controlled clinical studies. Methods: A double...

Ventilation inhomogeneity assessed by nitrogen washout and ventilation-perfusion mismatch by capnography in stable and induced airway obstruction.

Few studies have been published on gas distribution in the lung during acute and stable airway obstruction in children. Multiple breath nitrogen (N(2)) washout is an established method for assessing ventilation inhomogeneity, while the tidal breathing capnogram may be used as an indicator of ventilation-perfusion (V(')(A)/Q) mismatch. We hypothesized that significant V(')(A)/Q mismatch is not seen in stable airway obstruction unless obstruction is severe, and that stable and induced airway obstruction of similar severity would result in different degrees of V(')(A)/Q mismatch. To test this hypothesis, we performed spirometry measurements of forced expiratory volume in 1 sec (FEV(1)), multiple breath N(2) washout, and tidal breathing capnography in 11 young patients (9-30 years) with cystic fibrosis, 37 asthmatic patients (8-18 years), and 34 healthy subjects (7-20 years). Lung function was measured at rest, after airway obstruction induced by cold dry air hyperventilation or methacholine challenge, and after beta(2)-agonist treatment. V(')(A)/Q mismatch was assessed from the slopes of the phases II and III of the capnogram. We observed a normal capnogram during stable obstruction of moderate severity despite significant ventilation inhomogeneity. In patients with severe stable obstruction and in those with induced airway obstruction significant ventilation inhomogeneity and pathological capnograms were seen. Induced airway obstruction, resulted in a more pathological capnogram than stable obstruction of similar severity. beta(2)-agonist treatment reduced ventilation inhomogeneity, but did not improve the capnogram. Our findings are compatible with the presence of an efficient pulmonary blood flow regulatory mechanism that adequately compensates for chronic ventilation inhomogeneity of moderate severity, but not for severe or sudden airway obstruction.

Serum Eosinophil Cationic Protein and Bronchial Responsiveness in Pediatric and Adolescent Asthma Patients

Serum eosinophil cationic protein (ECP) has been promoted as a marker of inflammatory activity in bronchial asthma. Bronchial responsiveness, measured either by inhaling pharmacologically active substances such as histamine or methacholine, or by applying physical stimuli such as the hyperventilation of cold dry air, is also considered to be an indirect marker of bronchial inflammation. In this study, we investigated the possible relationship between serum ECP and bronchial responsiveness to both cold dry air and histamine in presently symptom- and medication-free pediatric and adolescent asthma patients. Thirty-six children and adolescents with atopic asthma were studied. On 2 consecutive days, bronchial responsiveness was assessed nonpharmacologically by cold dry air and pharmacologically by histamine in random order. Blood samples for determination of ECP were collected before each challenge. Serum ECP levels correlated with neither cold dry air-induced changes in FEV1 nor the provocation concentrations of histamine causing a 20% fall in FEV1. Subjects with bronchial hyperresponsiveness to cold dry air and histamine had somewhat higher levels of serum ECP than subjects with normal responses, but these differences were insignificant. Our results indicate a lack of relationship both between serum ECP and bronchial responsiveness to cold dry air and between serum ECP and bronchial responsiveness to histamine.

Circadian Variation in Allergen and Nonspecific Bronchial Responsiveness in Asthma

In a majority of patients, exacerbations of asthma occur more frequently during the night than day. Many hypotheses have been proposed to explain such variation in asthma. The airways of asthmatic persons are characterized by an abnormal degree of inflammation and bronchial hyperre-sponsiveness to both nonspecific and specific challenges. Studies of both children and adults with asthma document marked circadian rhythmicity in the response of airways to bronchial challenges with histamine, methacho-line, acetylcholine, saline, and house dust mite. Taken together, the findings of these investigations indicate that the hyperreactivity of airways to these agents is more profound and prolonged following evening and overnight tests compared to tests conducted in the midday and afternoon. The temporal pattern in bronchial response to the hyperventilation of cold dry air is different. The hyperresponsiveness of airways to this challenge is greatest in the afternoon. The amplitude of the circadian rhythm in airway hyperreactivity seems to be correlated to the amplitude of the circadian rhythm of pulmonary function; the greater the day-night difference in bronchial reactivity is, the greater is the day-night difference in flow rates.

Effect of a novel 5-lipoxygenase activating protein inhibitor, BAYx 1005, on asthma induced by cold dry air.

BACKGROUND: Leukotrienes have been implicated in the mediation of airway obstruction induced by hyperventilation of cold dry air in asthmatic subjects. The effect of a novel inhibitor of 5-lipoxygenase activating...

Influence of the duration of inhalation of cold dry air on the resulting bronchoconstriction in asthmatic subjects

Hyperventilation of cold dry air causes bronchoconstriction in asthmatic subjects and has been proposed as a test for assessing bronchial hyperresponsiveness. The influence of the duration of inhalation of unconditioned cold air has not been studied. We have investigated the question in 12 asthmatic subjects in a clinically stable state. Each subject underwent three inhalation tests at a maximum interval of two weeks. On each day, the duration of inhalation was different, being randomly 2, 3 or 4 min depending on the subject. Doubling doses of cold air produced by a freon conditioner were administered, increasing ventilation from 7.5 to 15, 30, 60 l.min-1 and maximum voluntary ventilation (MVV). Forced expiratory volume in one second (FEV1) was assessed after each period of cold air inhalation. The test was stopped when the FEV1 had decreased by 20% or more, or when MVV had been achieved. The dose of cold air expressed as the level of ventilation causing a 20% change in FEV1 (PD20) was interpolated from individual dose-response curves. Dose-response curves shifted to the left when the duration of ventilation was increased. PD20 was significantly lower after 3 min of ventilation than after 2 min (mean +/- SD PD20 of 41.7 +/- 1.4 l.min-1 compared with 53.3 +/- 1.2 l.min-1; p = 0.002). There was a further fall in PD20 after 4 min of ventilation (PD20 = 36.1 +/- 1.5 l.min-1) but the difference compared with the values obtained after 3 min was not significant (p = 0.09), thus suggesting a plateau.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Pharmacology of Nedocromil Sodium

In attempts to define the clinical pharmacological activity of inhaled nedocromil sodium, various challenge systems, ranging from specific antigen challenge to provocation with chemical irritants such as sulphur dioxide, have been used. A single dose (4 mg) of nedocromil sodium taken before antigen challenge prevented both early and late asthmatic responses, whereas the same dose taken shortly after the early response delayed onset of the late reaction but did not affect its magnitude. Exercise-induced asthma was inhibited by pretreatment with nedocromil sodium, as were the bronchoconstrictor responses to hyperventilation of cold dry air and inhalation of ultrasonically nebulised distilled water ('fog'). Mast cells lying in the surface mucosa of the lung are thought to be less stable in asthmatic subjects and may be implicated in the mechanism of response to these 3 types of physical insult. However, in addition to the marked protective action on isolated mucosal mast cells which has been reported from preclinical studies, nedocromil sodium was also effective against bronchoconstriction induced by sulphur dioxide in hyper-responsive asthmatic and atopic subjects. The response to sulphur dioxide, in which axon reflexes are thought to be involved, is less likely to have an immunological mechanism and it is clear that in this type of situation the effect of nedocromil sodium can be more readily differentiated from that of sodium cromoglycate. The increased potency and wider scope of activity described for nedocromil sodium suggests a therapeutic advantage for this new compound in chronic inflammatory allergic lung disorders.

Nonspecific bronchial hyperresponsiveness to inhaled histamine and hyperventilation of cold dry air in subjects with respiratory symptoms of uncertain etiology.

Fifty adult subjects referred to a respiratory function laboratory of a tertiary care hospital for respiratory symptoms of uncertain etiology were investigated prospectively by means of a questionnaire, isocapnic inhalation of dry cold air (-20 degrees C), histamine inhalation tests, monitoring of peak expiratory flow rates, total eosinophil counts, and total IgE. Wheezing, tightness in the chest, dyspnea, and cough were reported by 35, 23, 41, and 30 subjects, respectively. FEV1 values less than 80% pred were found in only 2 subjects. Twenty-nine subjects had a PC20 histamine less than or equal to 16 mg/ml. Twenty, 15, and 10% falls in FEV1 were found in 10, 18, and 26 subjects, respectively, using hyperventilation of cold air. Significant eosinophilia and increased total IgE levels were seen in 5 and 18 subjects, respectively. Eight subjects had daily changes in PEFR greater than 20% on at least 1 day of monitoring. There was no significant association between specific responses to the respiratory questionnaire or the presence of rhinitis on the one hand and bronchial responsiveness to histamine and cold air on the other hand. The 10 subjects who demonstrated a greater than 20% change in FEV1 after cold air inhalation also had a PC20 less than 16 mg/ml, and 5 of them reacted at a concentration less than or equal to 2 mg/ml. Two subjects who had a PC20 less than or equal to 2 mg/ml demonstrated a less than 20% change in FEV1 after inhaling cold air. There was no association between the increase in total eosinophils or IgE and bronchial hyperresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

321 Non-specific bronchial hyperresponsiveness to inhaled histamine and hyperventilation of cold dry air in individuals with respiratory symptoms on unknown etiology

321 Non-specific bronchial hyperresponsiveness to inhaled histamine and hyperventilation of cold dry air in individuals with respiratory symptoms on unknown etiology

317 Inhaled lidocaine does not significantly alter bronchial responsiveness to hyperventilation of cold dry air in asthmatic subjects

317 Inhaled lidocaine does not significantly alter bronchial responsiveness to hyperventilation of cold dry air in asthmatic subjects

Effect of cold and warm dry air hyperventilation on canine airway blood flow.

Tracheobronchial blood flow increases with cold air hyperventilation in the dog. The present study was designed to determine whether the cooling or the drying of the airway mucosa was the principal stimulus for this response. Six anesthetized dogs (group 1) were subjected to four periods of eucapnic hyperventilation for 30 min with warm humid air [100% relative humidity (rh)], cold dry air (-12 degrees C, 0% rh), warm humid air, and warm dry air (43 degrees C, 0% rh). Five minutes before the end of each period of hyperventilation, tracheal and central airway blood flow was determined using four differently labeled 15-micron diam radioactive microspheres. We studied another three dogs (group 2) in which 15- and 50-micron microspheres were injected simultaneously to determine whether there were any arteriovenous communications in the bronchovasculature greater than 15 micron diam. After the last measurements had been made, all dogs were killed, and the lungs, including the trachea, were excised and blood flow to the trachea, left lung bronchi, and parenchyma was calculated. Warm dry air hyperventilation produced a consistently greater increase in tracheobronchial blood flow (P less than 0.01) than cold dry air hyperventilation, despite the fact that there was a smaller fall (6 degrees C) in tracheal tissue temperature during warm dry air hyperventilation than during cold dry air hyperventilation (11 degrees C), suggesting that drying may be a more important stimulus than cold for increasing airway blood flow. In group 2, the 15-micron microspheres accurately reflected the distribution of airway blood flow but did not always give reliable measurements of parenchymal blood flow.

Diurnal variation in bronchial responsiveness in asthmatic children

To establish the presence of a diurnal variation in bronchial responsiveness in asthmatic children, the increase of peak expiratory flow rate (PEFR) following sympathomimetic inhalation and the response to bronchial provocation with histamine and hyperventilation of cold dry air (HVCDA) were studied. Twenty-nine patients (20 boys, nine girls, aged 9.3 to 17.8 years) measured PEFR before and after sympathomimetic inhalation three times a day for four weeks. A further 15 patients (eight boys, seven girls, aged 6.9 to 18.0 years) underwent bronchial provocation testing every six hours for 24 hours. A diurnal variation in bronchodilator responsiveness was demonstrated in 55% of the first group. Mean amplitude was 60.8% of patients' mean increase in PEFR following bronchodilators. On grouped data, bronchodilation was greater in the morning than in the afternoon (p less than 0.0005) or in the evening (p less than 0.0005). A diurnal variation in the response to bronchial provocation was also found in the second group, but the timing of the rhythm depended on the stimulus used. On grouped data, airways were most sensitive to histamine at 0400 hours and most sensitive to HVCDA at 1600 hours. The diurnal variation demonstrated in bronchial responsiveness could not be attributed to changes in baseline airway caliber and was present, despite the patients' taking sufficient medication to control their asthmatic symptoms.

Reproducibility of hyperventilation of cold dry air in children with cystic fibrosis.

Wheezing is a significant problem in some patients with cystic fibrosis. Currently available tests are not reliable at determining whether this wheezing is due to co-existent asthma or to the underlying pulmonary disease. The reproducibility of hyperventilation of cold dry air (HVCDA) was studied over eight days in 11 children with cystic fibrosis. A group with mild lung disease were selected to minimize the variability due to underlying pulmonary disease. Fifty-six per cent of subjects had consistent responses to HVCDA. A test of reproducibility was performed on the respiratory heat exchange, the percentage fall in FEV1 after HVCDA and the ratio of these two (R). Respiratory heat exchange was found to be highly reproducible with a reproducibility co-efficient of 0.97. The percentage fall in FEV1 after HVCDA and R were not reproducible over the eight-day period. Hyperventilation of cold dry air did not give reproducible results in children with cystic fibrosis, suggesting that a single test may not be suitable for judging bronchial liability.

Airway responses to hyperventilation of cold dry air: Duration of protection by cromolyn sodium

The magnitude and duration of the inhibitory effect of three doses of cromolyn sodium on the airway response to hyperventilation of cold dry air was examined in a double-blind, randomized controlled trial. Eight subjects with well controlled asthma were studied. On 4 separate days, doses of either 2 mg, 10 mg, 20 mg, or placebo were administered by metered-dose inhaler. Twenty minutes, 2 hours, and 4 hours after each medication, airway responsiveness to isocapnic hyperventilation of cold dry air was measured by use of a standardized dose-response method. At 20 minutes, all three doses inhibited bronchoconstriction, and there was no evidence of any difference in the magnitude of the inhibition between the doses. All three doses progressively provided less protection with time. By 2 hours, the inhibition induced by 2 mg was no longer different from placebo, and by 4 hours, only 20 mg still provided significant protection. The results demonstrate that, although the initial magnitude of inhibition may not be different between 2 mg and 20 mg, the rate at which the protective effect wears off is dose related.

Equipment to condition inspired air over a wide temperature and humidity range for a hyperventilation challenge for asthmatics

Most, if not all, asthmatics suffer bronchoconstriction following hyperventilation of cold dry air. The mechanics of the response is not known but may be due to either airway cooling, airway moisture loss, vagal nerve reflex action, hyperpnoea, or a combination of these factors. Further work is required to isolate which factors are involved in the processes leading to the asthma attack. To do this, it is necessary to study the responses of asthmatics to hyperventilation of air at various temperatures, water content and minute-ventilation levels. The equipment described in the paper is capable of conditioning air over a temperature range of −20°C to +40°C and water content from dry to fully saturated. It is designed to be cleanable and is manufactured from materials which will not corrode.

Control of expired CO 2 level and minute-ventilation during a hyperventilation challenge for asthmatics

Hyperventilation of cold dry air initiates bronchospasm in most if not all asthmatics. The hyperventilation challenge is a useful means of studying asthma and the evaluation of anti-asthma drugs and treatments; two key elements of such a challenge are the means of achieving a target minute-ventilation and the maintainance of constant arterial CO 2 levels during hyperventilation. The author describes a simple cold air eucapnic hyperventilation challenge which allows a subject to hyperventilate to a predetermined target minute-ventilation whilst maintaining a constant expired level of CO 2.