Cold Air Challenge Research Articles

Efficacy of formoterol metered aerosol in children

To evaluate the effect of formoterol MDI (F) in the treatment of bronchial childhood asthma, five studies were performed in a total of 66 young asthmatics. In single-dose studies with 12 micrograms, F showed a rapid onset of action and in comparison to salbutamol a four-times-longer-lasting bronchospasmolytic effect (BSL). In addition, we looked at the BSL and the protective effect (P) in exercise-induced asthma (EIA) after 6, 12, and 24 micrograms. The BSL was not significantly different with respect to onset, magnitude, and duration of action, nor was the P, yet the latter seemed to be superior at 2 and 8 h after 24 micrograms. In a long-term study with 2 X 12 micrograms the patients' clinical well-being could be improved while drug consumption decreased. During another 3-month monotherapy with 2 X 12 micrograms the P in histamine- and cold air challenge was investigated and compared to prestudy values. It could be shown that long-lasting BSL and P did not diminish. Furthermore, there is evidence to suggest an improvement of bronchial hyperresponsiveness after withdrawal of F.

Cold Air Challenge and Platinum Skin Reactivity in Platinum Refinery Workers: Bronchial Reactivity Precedes Skin Prick Response

An investigation of a platinum refinery operation consisted of an administered questionnaire, spirometry, skin prick testing with platinum salts and common aeroallergens, serum total IgE, radioallergosorbent test for platinum salts, and measurement of nonspecific airway hyperresponsiveness by cold air challenge testing. Among 136 employees examined, there were 107 current and 29 medically terminated workers; 23 (17 percent) subjects had a positive platinum salts prick skin test and 19 (14 percent) displayed a positive cold air challenge. RAST binding for platinum salts IgE antibodies showed a high level of agreement with platinum skin prick test results. A proportion (63 percent) of the population (74 current and 12 terminated workers) underwent repeat platinum skin testing one year later. Among current workers, there was conversion of the platinum skin test from negative to a positive test in five employees, with three conversions occurring in workers who showed only a positive cold air challenge test the year before. Platinum skin sensitivity, asthma symptoms, and nonspecific airway hyperresponsiveness persisted for years after termination of exposure in some medically terminated workers presumably because of a delay in removal from work of employees who became sensitized to platinum salts. It is suggested that proper surveillance for occupational asthma involves the use of several testing procedures. Prompt removal from work of individuals found to become sensitized to platinum salts is important in this industry.

Early Airway Obstruction in Young Asymptomatic Smokers after Cold-Air Challenge

In 10 asymptomatic young smokers and 15 non-smokers, total respiratory impedance was determined by means of the forced oscillation technique in a frequency range between 4 and 52 Hz under basal conditions, and after isocapnic hyperventilation with cold air. In non-smokers, cold-air inhalation caused a statistically significant increase in respiratory resistance between 8 and 28 Hz, and post-challenge reactance values decreased at almost all frequencies. In smokers, respiratory resistance increased at almost all frequencies, but most markedly at lower frequencies in the range from 8 to 28 Hz; respiratory resistance decreased with increasing frequency. Respiratory reactance decreased significantly between 8 and 36 Hz. Comparing the smokers and non-smokers, respiratory resistance and reactance were not significantly different under basal conditions. However, after cold-air challenge, respiratory resistance was significantly higher between 8 and 16 Hz, and respiratory reactance significantly lower between 8 and 40 Hz. It is concluded that after cold-air challenge, a broncho-constricting effect extending largely into the small peripheral airways can be demonstrated by impedance measurement in a group of asymptomatic young smokers which is not observed in normal subjects. Therefore, this method is very useful for the early detection of mechanical abnormalities induced by smoke inhalation.

Cross‐sectional study of platinum salts sensitization among precious metals refinery workers

A cross-sectional medical evaluation was conducted to determine respiratory and dermatological effects of platinum salts sensitization among workers in a secondary refinery of precious metals. Fifteen of 107 current employees and eight (28%) of 29 former employees, who had been terminated from employment on average for 5 years because of respiratory symptoms, had positive skin reactivity to platinum salts. Platinum salts skin reactivity was significantly associated with average air concentrations of platinum salts in employees' present work area. Workers with positive platinum salts skin tests had significantly higher prevalences of reported rhinitis, asthma, and dermatitis than negative skin test workers. They also had increased bronchial response to cold air challenge and elevated levels of total serum IgE. Platinum salts sensitization was not associated with atopic tendency as measured by sensitivity to common aeroallergens, but was strongly associated with cigarette smoking status. The findings indicate that cigarette smoking may be a risk factor for the development of platinum salts allergy. The persistence of platinum salts sensitization and high prevalence of adverse health outcomes among former workers demonstrate the importance of regular medical monitoring so that sensitized workers can be removed from exposure before they develop long-term health problems.

The relationship between longitudinal change in pulmonary function and nonspecific airway responsiveness in children and young adults.

The relationship between airway hyperresponsiveness and longitudinal change in lung function was assessed in a population-based sample of 184 children and young adults observed over a maximum span of 12 yr. Pulmonary function was assessed annually with spirometry, and health and household information was obtained with standardized questionnaires. Nonspecific airway responsiveness to eucapneic hyperventilation with subfreezing air was measured on at least two occasions between the sixth and twelfth annual surveys. At any given survey, a significant bronchoconstrictor response was defined as [( prechallenge FEV1-postchallenge FEV1]/pre-FEV1) greater than or equal to 0.13, a value that identified 10% of the population. Subjects were classified as "never", "always", or "inconsistent" responders according to the consistency of responsiveness determined in different surveys. Subjects were classified further as "labile" if their maximal survey-to-survey difference in delta FEV1/FEV1 was greater than or equal to 0.18, and as "nonlabile" otherwise. A Markov-type autoregressive model that adjusts for previous pulmonary function level, sex, growth variables, and smoking exposures was used to model growth of FEV1, FEF25-75, and FVC. Overall, 135 (73%) of subjects never responded to the cold air challenge, six (3%) always responded, and 43 (24%) responded on one but not all occasions. Levels and rates of increase in level of FEF25-75 were significantly lower in the inconsistent and always responders. In contrast, levels of FVC were greatest and increased most in the always responders. In labile subjects, both FEF25-75 and FEV1 growth rates were reduced. These effects persisted when asthmatics were excluded from the analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Longitudinal variability in airway responsiveness in a population-based sample of children and young adults. Intrinsic and extrinsic contributing factors.

The degree and long-term variability of airway responsiveness to eucapneic hyperventilation with cold air was assessed in 287 children and young adults (less than 23 yr of age) (735 challenge tests) enrolled in a longitudinal study of pulmonary function, 179 of whom underwent two to five cold-air challenge tests between 1982 and 1986. Survey-to-survey variability in airway responsiveness was assessed with computation of adjusted within-subject correlation coefficients for continuous measures of response (percent decrease in FEV1 after challenge) and with adjusted odds ratios for dichotomous outcomes ("positive" if percent decrease FEV1 greater than or equal to 0.13). The relationships between variability in responsiveness and the following variables were examined: age, baseline level of pulmonary function, presence of respiratory symptoms and illnesses, smoking exposures, season, level of ventilation achieved during testing, and temperature of the expired air. Airway hyperresponsiveness was demonstrated consistently over all surveys in only six of 49 (12%) subjects who had ever demonstrated a "positive" airway response. The odds relating positive responses between surveys was 12.1 for airway hyperresponsiveness, 21.5 for "persistent" wheeze, and 6.7 for "any" wheeze. Significant predictors of airway hyperresponsiveness were wheeze symptoms (OR = 2.3), hay fever (OR = 1.6), and a chest illness requiring bed rest (OR = 2.5). Adjustment for survey-to-survey differences in respiratory symptoms, or for differences in testing conditions between surveys, did not alter the observed variability in airway responsiveness. Adjustment for "random error" (assessed with replicate measures of airway responsiveness in a subsample of 21 subjects) improved the observed survey-to-survey variability by 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoprovocation Testing

Bronchial hyperresponsiveness is a constant feature of asthma even when airflow obstruction is absent. Detecting nonspecific bronchial hyperresponsiveness is useful when the diagnosis of asthma has not been confirmed or when a patient describes symptoms of cough, chest tightness, and dyspnea that cannot be ascribed to other causes. Also, because wheezing is a symptom of other disorders, inhalation challenge tests can be useful in defining its cause when reversible airflow obstruction has not been documented. A number of easy and safe techniques are available to detect nonspecific bronchial hyperresponsiveness. The histamine and methacholine challenge have had the most widespread use in the clinical pulmonary function laboratory. The exercise and cold air challenges are limited by expense. The osmotic challenge may gain more acceptance as experience with this technique grows. These different agents have the advantage of simplicity, reproducibility, a low number of adverse effects, and a high degree of specificity and sensitivity. A limited number of asthmatics show bronchial hyperresponsiveness to specific agents such as chemical sensitizers in the workplace, aeroallergens, aspirin, nonsteroidal anti-inflammatory agents, and sulfiting agents. Bronchoprovocation testing with these agents is usually reserved for the hospital laboratory because severe or delayed reactions may occur. These tests, however, can be extremely useful in defining a population of sensitive asthmatics.

Comparison of Ultrasonically Nebulized Distilled Water and Cold-air Hyperventilation Challenges in Asthmatic Patients

Cold-air hyperventilation (CAHC) and ultrasonically nebulized distilled water (UNDW) challenges were compared in 11 asthmatic patients who were moderately sensitive to methacholine. The challenges were performed on two separate days within one week of each other. Baseline FEV1 on each test day was greater than 70 percent of predicted. Ten of 11 subjects' FEV1 decreased at least 15 percent, and nine of 11 decreased at least 20 percent during the UNDW. Ten of 11 subjects' FEV1 decreased at least 10 percent, and eight of 11 decreased at least 15 percent during the CAHC. Using a Spearman rank coefficient, the results of the CAHC and UNDW were compared; the best correlation between the various CAHC and UNDW measurements equaled only 0.51. The correlation between UNDW and CAHC suggests that the mechanism of action of each challenge may be different.

Airway reactivity as determined by a cold air challenge in infants with bronchopulmonary dysplasia

Bronchopulmonary dysplasia, a common complication of ventilatory support in neonates, is characterized by low pulmonary compliance, increased pulmonary resistance, and limitations to airflow. 1,2 Bronchospasm has been demonstrated in some of these infants by their response to pharmacologic bronchodilation. 3,4 In older children, this reactivity of the airway may be provocatively induced by medications or cold air inhalation. 5,6 Clinical symptoms have often been suggestive of reactive airway disease 9 3.7. 8 In this article we report the technique of a modified cold air challenge test to determine airway reactivity in low birth weight infants. Infants with BPD, at term postconceptional age, were specifically evaluated for evidence of airway reactivity and compared with postconceptional age-matched preterm infants without BPD.

Theophylline Minimally Inhibits Bronchoconstriction Induced by Dry Cold Air Inhalation in Asthmatic Subjects

The aim of this study was to evaluate the effect of a sustained-release theophylline preparation on bronchial responsiveness to cold dry air inhalation in asthmatic subjects. Sixteen adult subjects with asthma in a clinical steady state underwent 3 isocapnic cold air challenges on 3 consecutive days at a time when they had not received oral theophylline medication over the past 3 days. The dose of cold air causing a 20% (PD20) fall in FEV1 was obtained from each subject's dose-response curve. Subjects were then administered active or placebo sustained-release theophylline preparations according to a double-blind, randomized, two-treatment crossover design. Medication was given for a minimum of 3 consecutive days. PD20 was reassessed on 4 different days, 3 to 4 h after receiving active or placebo medication (two visits for each medication). We found a significant bronchodilator effect of theophylline as compared to the placebo (mean +/- SD differences in changes of FEV1 of 8.8 +/- 1.9%). We also documented a significant blocking effect of the active medication as opposed to the placebo on PD20 (p = 0.01). This difference (mean = 0.18 on the loge scale) was statistically beyond the intraindividual between-day variability observed on the 3 control days (p less than 0.001) but was physiologically minimal. This blocking effect was also partially related to changes in airway caliber. We conclude that theophylline showed a blocking effect on bronchial responsiveness to dry cold air, which was physiologically minimal and was partially related to changes in airway caliber.

Exercise-induced asthma.

Though exercise-induced asthma (EIA) has been recognized for centuries, its characteristics, standardized testing, and pharmacologic management have been clarified only in the last two decades. Controversy continues concerning etiology; whether or not cold air, hypertonic and hypotonic bronchial challenges involve the same mechanism(s); and the incidence and clinical significance of late phase reactions. Aerosolized adrenergic agents such as albuterol or terbutaline, when administered prior to exercise, are usually effective in preventing EIA. Theophylline varies in effectiveness from subject-to-subject as does cromolyn sodium. Other agents such as H-1 antihistamines, ipratropium bromide, calcium channel blockers and adrenocorticosteroids are less effective when used alone, but may be useful when used in association with the more potent drugs.

460 The relationship between atopy and the response to cold dry air (CDA) and histamine (H) challenge in perennial rhinitis (PR)

460 The relationship between atopy and the response to cold dry air (CDA) and histamine (H) challenge in perennial rhinitis (PR)

Cold air challenge in children with asthma.

A study was designed to determine the sensitivity and specificity of a cold air bronchial provocation test. A total of 18 children with asthma (mean age 12 years) and 18 normal children (mean age 14 years) were studied. The cold air challenge consisted of a 4 min period of isocapnic hyperventilation of subfreezing air (mean temperature -15 degrees C). In-Induced response in forced expiratory volume in 1 sec (FEV1) expressed as a percentage of predicted normal values was obtained at 4, 6, and 8 min post-challenge. The average response to the cold air was a 27% decrease of FEV1 in asthmatics, which was significantly different from that of the normal children, who showed no statistically significant drop. In both the asthmatic and normal groups, the maximal drop in FEV1 had occurred by the time measurements 4 min post-challenge had been made. At that time, the smallest overlap was observed between normal and asthmatic children. This suggests that the fourth minute post-challenge can be chosen as a cut-off time to distinguish normal from asthmatic children. Considering a decrease of FEV1 greater than 10% as a positive test, the sensitivity of the cold air challenge was 95% and the specificity was 89%.

Cold air challenge of airway hyperreactivity in children: Dose-response interrelation with a reaction plateau

A previous study of cold air challenge (CACh) in children with asthma produced indirect evidence for the existence of a reaction plateau. To examine directly this phenomenon, 17 children, mean age 13 1/2 years, were challenged by isocapnic hyperventilation with -10 degrees C air at 75% of maximal voluntary ventilation for 10 minutes (extended CACh [ECACh]). Each minute FEV1 and maximum expiratory flow at 25% remaining vital capacity (V25) were measured. During "recovery" these measurements were repeated every minute for 10 minutes. Analysis of the cumulative dose-response curves constructed from the measurements revealed that a reaction plateau was reached in the last minutes of the challenge by both functions in each child. Induced changes in absolute terms were similar for both functions (FEV1: -28 +/- 12% predicted; V25: -29 +/- 17% predicted), but V25 started at a lower baseline (FEV1: 81 +/- 15% predicted; V25: 48 +/- 27% predicted) and thus arrived at a higher degree of obstruction (FEV1: 53 +/- 19% predicted; V25: 19 +/- 13% predicted). Together with the reaction plateau developing faster for V25, this indicated a dose-response influenced by baseline small airway obstruction. Although the size of the reaction differed from one child to the other (FEV1: -5% to -50% predicted; V25: -4% to -77% predicted), interindividual variability in the development of the reaction decreased toward the end of the challenge and was minimal at the plateau and in the early minutes of "recovery."(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic Asthma Due to Toluene Diisocyanate

Twelve subjects were studied with inhalation challenge testing to toluene diisocyanate (TDI) because of suspected TDI asthma based on a consistent clinical and occupational history. In seven cases, TDI asthma was documented by a positive inhalation challenge to low levels of TDI. Six of the seven TDI reactors had persistent respiratory symptoms and required daily treatment even though they had been removed from isocyanate exposure for intervals as long as 12 years (mean 4.5 years). These six TDI reactors had either dual (four cases) or late bronchospasm (two cases) to less than 20 ppb TDI, and all had a positive methacholine or cold air challenge prior to study. The one TDI reactor with a negative methacholine challenge had a positive (immediate) bronchospastic response to a TDI challenge performed one week after removal from isocyanate exposure. Five workers had a negative TDI challenge, two of whom had persistent respiratory symptoms and positive methacholine challenges at the time of TDI inhalation testing. We conclude that respiratory symptoms may persist following long-term removal from occupational exposure to TDI and are associated with nonspecific bronchial hyperreactivity. The TDI sensitivity may also persist for a long time even in the absence of any additional occupational exposure. Long-term prospective studies of symptomatic isocyanate workers are needed to fully define the extent of this problem.

Within- and between-day reproducibility of isocapnic cold air challenges in subjects with asthma

Eight adult subjects with asthma had isocapnic cold air challenges on 4 different days. Three consecutive tests were performed on each visit with functional recovery between tests. Subjects were asked to breathe dry cold air (−20 °C) for progressively increasing levels of minute ventilation (7.5, 15, 30, and 60 L/min and maximal voluntary ventilation) until a 20% fall in FEV 1 had been reached or when maximal voluntary ventilation was done. FEV 1 was assessed between each level. The doses of respiratory heat exchange and minute ventilation causing 10%, 15%, and 20% changes in FEV 1 were interpolated from dose-response curves. The within-and between-day 95% confidence intervals based on a single determination on the log e scale varied from ±0.32 to 0.59 for the indices derived from respiratory heat exchange. Reproducibility of the between-day results was more satisfactory than for the corresponding within-day assessments. No significant within-day tachyphylaxis was demonstrated for these indices.

Approaches to assessing pulmonary dysfunction and susceptibility in workers.

Indices of the maximal forced expiration are the most widely adopted method of screening for occupational lung disease because of their ease of measurement, employee acceptability, and reproducibility. However, these indices may lack sensitivity, specificity, or validity in detecting cases of some occupational lung diseases at asymptomatic stages when intervention may affect outcome. In populations at increased risk for occupational asthma, pneumoconiosis, or hypersensitivity pneumonitis, three other types of screening are being evaluated in field settings: tests for bronchial hyperreactivity, barriers to diffusion, and abnormalities in gas distribution in the lung. The potential methods of screening--cold air challenge, methacholine challenge, peak flow logs, diffusing capacity, and single breath nitrogen tests--await clinical trials in industrial settings to evaluate whether early case finding of susceptible subjects can result in prevention of morbidity.

Reduced hyperpnea-induced bronchospasm following repeated cold air challenge.

This study assessed reduction in expiratory function in 12 asthmatic subjects both after 5 min of cold air provocation (CAP) with dry air conditioned to approximately 0 degrees C and after exercise (to 85% of predicted maximum heart rate) while breathing ambient room air (approximately 21 degrees C and 40% relative humidity). These assessments were done both before and after the following training protocol. Three 5-min periods of isocapnic cold air hyperpnea separated by 5-min rest periods were performed breathing 0 degrees to -10 degrees C air, for 36 sessions over 12 wk. As expected, pretraining expiratory function was significantly reduced (P less than 0.001) after both CAP and exercise. The posttraining reduction in expiratory function after CAP and exercise, however, was significantly less pronounced (largest P less than 0.05). These data support our hypothesis that repeated bouts of cold air challenge result in airway acclimatization to cold air and consequent decrease in exercise-induced bronchospasm. Acclimatization may result directly either by habituation of the airways or by vasodilation leading to increased bronchial blood flow and consequent reduced airway cooling. An unanticipated finding, though, is that repeated cold air challenge may also cause long-term inflammatory changes in the airways. A significant percentage of subjects experienced reduced base-line pulmonary function and overall exacerbation of asthma symptoms during the training period.

Cold air provocation of airway hyperreactivity in patients with cystic fibrosis.

Thirty-four patients with cystic fibrosis (CF) were assessed for baseline pulmonary functions before, and 5 and 15 minutes after cold air challenge (CACh). Most of the patients had no change in forced expiratory volume in 1 second (FEV1) and maximum expiratory flow at 25% vital capacity (Vmax25%VC) post-CACh. Five patients responded with reduced FEV1 and 13 with reduced Vmax25%VC. However, paradoxical increases were noted in 10 patients for FEV1 and in 5 for Vmax25%VC. Paradoxical responses were most frequent in patients with severe lung disease. The explanation for this variability may lie in the varying degrees of airway instability and volume of airway contribution (VAC) to early flows, resulting from the damage caused by chronic infection. Conventional challenges may be useless in determining the true incidence of bronchial hyperreactivity in patients with CF.

Comparison of cold air, ultrasonic mist, and methacholine inhalations as tests of bronchial reactivity in normal and asthmatic children

The sensitivity and specificity of cold air, ultrasonically nebulized distilled water mist (USM), and standard methacholine (MCH) challenges were studied in 21 children with asthma (mean age 11.5 years) and 12 normal children (mean age 14.2 years). The cold air challenge consisted of successive 3-minute periods of hyperventilation during which incremental volumes of subfreezing air (mean temperature -16 degrees C) were inhaled. To perform the USM challenge, subjects inhaled increasingly larger volumes of nebulized distilled water while breathing tidally. The specificity of both nonpharmacologic challenges was found to be 100%, whereas that of MCH was only 83%. The sensitivity of the cold air and USM tests was 57% and 71%, respectively, compared with 95% obtained with MCH challenge. We conclude that cold air and USM challenges are promising alternatives to the MCH challenge, and may be superior to it if optimal standard testing protocols are defined.