Cold Dry Air Challenge Research Articles

A Pilot Study Investigating Clinical Responses and Biological Pathways of Azelastine/Fluticasone in Nonallergic Vasomotor Rhinitis before and after Cold Dry Air Provocation

Background: Nonallergic vasomotor rhinitis (NAVMR) has been considered a diagnosis by exclusion due to unknown mechanisms or lack of diagnostic biomarkers. Methods: To determine clinical responses and biological pathways in NAVMR subjects challenged to cold dry air (CDA) in an environmental exposure chamber (EEC) pre- and posttreatment with azelastine/fluticasone (AzeFlu), 30 NAVMR subjects, prescreened for CDA-induced symptoms (approx. 14°C, <15% relative humidity, ×1 h) were randomized to treatment with AzeFlu (n = 20) or placebo (n = 10) for 2 weeks. Total nasal symptoms scores, minimum cross-sectional area, cough, and conjunctival redness were recorded at visit 1 (pretreatment) and visit 2 (posttreatment) before, during, and after CDA challenge. At both visits, nasal lavage fluid (NLF) and nasal scrapings (NS) were collected pre- and post-CDA challenge. Substance P, neurokinin-A, and calcitonin gene-related peptide concentrations in NLF were analyzed pre- and postchallenge at each visit. Their relationship with CDA-induced symptoms was determined by statistical analysis. MicroRNA sequencing from NS determined differentially expressed miRNA between the treatment groups post-CDA challenge at each visit. Results: The minimum cross-sectional area (p < 0.05), cough count (p < 0.05), and substance P (p < 0.01) improved posttreatment with AzeFlu versus placebo. Gene targets for differentially expressed miRNAs at visit 1 were enriched for biological pathways regulating epithelial ciliogenesis and cell integrity that were modified in the AzeFlu-treated group versus placebo posttreatment. Conclusions: This study demonstrated the feasibility of an EEC model to investigate CDA-induced clinical responses and pathobiology in NAVMR subjects pre- and posttreatment with AzeFlu. NAVMR disease mechanisms for other nonallergic triggers can be investigated similarly.

Small airway function before and after cold dry air challenge in pediatric asthma patients during remission.

We wanted to compare cold dry air challenge (CACh) induced changes in spirometric parameters with changes in nitrogen multiple breath washout (N2 MBW) parameters in pediatric asthma patients during clinical remission over the past year (ie, with "inactive asthma"). As N2 MBW assesses ventilation heterogeneity we expected to gain detailed information about peripheral airways contribution. In subjects with normal spirometry N2 MBW, spirometry and body plethysmography were performed at baseline, after CACh, and after salbutamol inhalation. An initial measurement of the fraction of exhaled nitric oxide (FeNO) was conducted. Forty-three (20 female) subjects, mean age 13.7 years (range 6.5-18.6) performed reproducible N2 MBW measurements. Ten were tested hyperresponsive (23.3%) and 33 normoresponsive (76.7%). Baseline spirometry and body plethysmography as well as FRC (N2 MBW) were similar in both groups. Scond (0.031 vs 0.022), Sacin (0.057 vs 0.067), and FeNO (92.0 vs 28.5 ppb) were not statistically different between hyperresponsive and nomoresponsive subjects at baseline. Subjects with airway hyperresponsiveness (AHR) showed significant increases in lung clearance index (LCI, P = 0.011) and Scond (P = 0.008) after CACh, and significant decreases after salbutamol (LCI: P = 0.005; Scond: P = 0.005). In contrast, normoresponsive subjects showed no relevant changes after CACh, and only a decrease of Scond after salbutamol (P = 0.007). There were significant correlations between the CACh induced changes in FEV1 and changes in LCI (r = -0.45, P = 0.003), Scond (r = -0.30, P = 0.047), and Sacin (r = -0.47, P = 0.008), respectively. Our study provides evidence of small airway involvement in children and adolescents with inactive asthma and airway hyperresponsiveness.

TRPV1 inhibition does not prevent cold dry air-elicited symptoms in non-allergic rhinitis

The transient receptor potential vanilloid 1 (TRPV1)-expressing sensory C-fibers may play a role in the development of nasal hyper-responsiveness and symptoms of non-allergic rhinitis (NAR). To evaluate the effects of a TRPV1-antagonist, SB-705498, on cold dry air (CDA)-induced symptoms in patients with NAR. This randomized, double-blind, placebo-controlled, crossover study evaluated 14 days of once daily, topical intranasal SB-705498 12 mg in 40 patients with NAR using a CDA challenge experimental model in an environmental exposure chamber (EEC, Cetero Research, Mississauga, Ontario). The primary endpoint was total symptom score (TSS), expressed as weighted mean over 60 minutes (WM0-60) or maximum TSS at 1 hour and 24 hours postdosing. Treatment with SB-705498, relative to placebo, did not improve WM0-60 or maximum TSS at 1 hour and 24 hours post-dosing on days 1 or 14. Mean (95% CI) treatment differences (SB-705498 - placebo) on day 14 were, for WM0-60 at 1 hour: -0.12 (-0.60, 0.36); for maximum TSS at 1 hour: -0.03 (-0.58, 0.51). SB-705498 had no impact on any other efficacy parameters. SB-705498 was well tolerated and pharmacokinetics analysis supported the dosing regimen. SB-705498 12 mg for 14 days did not alleviate the CDA-induced symptoms of NAR. Despite engagement of the TRPV1 receptor, there was no translation to clinical efficacy, suggesting redundancy in symptom pathways.

Nasal Provocation Test Using Allergen Extract versus Cold Dry Air Provocation Test: Which and When?

Nasal provocation tests (NPTs) are useful for evaluation of patients with allergic rhinitis. The cold dry air (CDA) provocation test is useful for evaluation of patients with nonspecific nasal hyperreactivity (NHR). This study aimed to determine whether the NPT or CDA provocation would be more useful for patients with different clinical pictures. We evaluated changes in nasal symptoms (visual analog scale [VAS]) and acoustic parameters after NPT or CDA provocation in healthy volunteers (group A, n = 27), patients with allergic rhinitis (group B, n = 20), and subjects with nonallergic rhinitis (group C, n = 26). According to their subjective cold hyperresponsiveness (SCH), we compared changes in VAS and acoustic parameters after each protocol. The correlation between results of the skin-prick test (SPT) and changes in VAS after each protocol was analyzed. Finally, we performed an analysis of correlation between NPT and CDA provocation. After NPT, group B showed a larger change in VAS for rhinorrhea, sneezing, and itching (p < 0.01). After CDA challenge, the change in VAS for nasal obstruction was larger in group C (p < 0.05). Changes in acoustic parameters were larger in groups B and C after NPT (p < 0.01). After CDA challenge, the SCH(+) group (n = 49) showed a larger decrease of acoustic parameters than the SCH(-) group (n = 24; p < 0.01). Significant correlation was observed between the size of SPT and degree of change in VAS after NPT. No significant correlation was observed between NPT and CDA. CDA could be an adjunct tool for evaluating NHR in patients with self-reported SCH.

Short‐time cold dry air exposure: A useful diagnostic tool for nasal hyperresponsiveness

Demonstration of nasal hyperreactivity (NHR) in allergic and nonallergic rhinitis remains a diagnostic challenge because of the lack of a clinically attractive protocol with high sensitivity and specificity. Our aim was to evaluate the feasibility of a shortened cold dry air (CDA) provocation protocol for the diagnosis of NHR in patients with allergic rhinitis (AR) and idiopathic rhinitis (IR). Twelve AR patients, 12 IR patients, and 12 controls were exposed to air at -10°C and <10% humidity for 15 minutes. Nasal symptoms were subjectively evaluated by visual analogue scale (VAS), and nasal obstruction was objectively measured by peak nasal inspiratory flow (PNIF) before and after CDA exposure. NHR was defined as a drop in PNIF larger than 20% from baseline upon CDA challenge. Nasal CDA exposure induced nasal obstruction in AR and IR patients but not in controls. The VAS for nasal obstruction increased significantly in IR patients (post-CDA: 9.1 cm [6.9, 9.7] vs. pre-CDA: 5.5 cm [5.0, 8.9], P = .004) as well as in AR patients (post-CDA: 5.0 cm [1.3, 6.6] vs. pre-CDA: 0.8 cm [0.0, 1.7], P = .001). PNIF values showed a significant decrease in the AR (post-CDA: 50.0 L/min [37.5, 97.5] vs. pre-CDA: 95.0 L/min [52.5, 127.5], P = .002) and IR (post-CDA: 75.0 L/min [47.5, 102.5] vs. pre-CDA: 100.0 L/min [67.5, 130.0], P = .002) group after CDA provocation, which was not observed in the controls (P = 1.000). The sensitivity and specificity of CDA provocation for diagnosis of NHR were 66.7% and 100%, respectively, for both IR and AR. In contrast to nasal obstruction, rhinorrhea and sneezing were not induced by CDA exposure. This study demonstrates that a short nasal CDA exposure is a reliable method for the diagnosis of NHR in rhinitis patients, with a high sensitivity and specificity.

Abstracts

Bronchodilatation and Bronchoprotection in Asthmatic Preschool Children from Formoterol Administered by Mechanically Actuated Dry-Powder Inhaler and Spacer; Nielsen, K.G., Bisgaard, H.; Am. J. Resp. Crit. Care Med. 2001, 164, 256–259.Background. Young asthmatic children have a specific need for more prolonged duration of bronchodilatation and bronchoprotection than is provided by intermittent therapy with short-acting beta-agonists. This is particularly true since young children are often under the care of others for large parts of the day. Inhaled Formoterol has a rapid onset of action, within a few minutes after inhalation, maximum effect at 30 minutes and sustained bronchodilatation and bronchoprotection for over 12 hours.Objective. The objective was to evaluate the bronchodilatory and bronchoprotective efficacy of long-acting beta-agonist Formoterol, delivered as a dry-powder from a mechanically actuated dry-powder inhaler with a spacer.Clinical Population. The clinical population included 12 asthmatic children, ages 2 to 5 years.Clinical Protocol. Lung function was evaluated using specific airway conductance in a whole body plethysmograph. Cold dry air challenge with hyperventilation was used as a bronchial challenge, and the responsiveness was estimated as a change in the specific airway resistance. Bronchoprotective effect of Formoterol Turbohaler 9 mcg was compared with Salbutamol 200 mcg and placebo at 15 minutes, 4 hours, and 8 hours post dose in a randomized, double-blind, placebo-controlled crossover study. All treatments were delivered from a DPI “Turbohaler” actuated mechanically into a spacer.Clinical Findings. Formoterol and Salbutamol produced similar and significant bronchodilatation at the first measurement, at 3 minutes post dose. Formoterol, however, offered persistent and stable bronchodilatation for at least 8 hours, while Salbutamol produced significant bronchodilatation for less than 4 hours. Formoterol produced significant bronchoprotection of 80% for at least 8 hours. The bronchoprotection from Salbutamol lasted less than 4 hours.Conclusions. The conclusions of the authors were that Formoterol administered via dry-powder inhaler with a spacer in a single dose produced rapid (approximately 3 to 5 minutes onset) and sustained bronchodilatation (up to 12 hours) and clinically significant bronchoprotection for at least 8 hours in 2- to 5-year-old asthmatic children. This investigation further suggests that using a spacer is an effective way to deliver aerosol in young asthmatic children.Reviewer's Comments. While Formoterol is exciting in terms of its pharmacodynamic properties, its delivery system is less than optimal when compared with ease of use of a Salmeterol discus haler. The introduction of a spacer here adds further mechanica1 obstacles, particularly for young children who are 2 to 5 years of age. However, the pharmacokinetic properties, i.e., the bronchoprotection and the bronchodilatation lasting up to 12 hours, is a useful modality when considering young children who are often in day care or nursery school for a large proportion of the day.Christopher Randolph, M.D. Waterbury, CT

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...

Function of pulmonary neuronal M(2) muscarinic receptors in stable chronic obstructive pulmonary disease.

Anticholinergic drugs often cause a considerable degree of bronchodilation in patients with chronic obstructive pulmonary disease (COPD). Pulmonary neuronal M(2) muscarinic receptors function to limit the magnitude of vagally induced bronchoconstriction. We hypothesized that the effectiveness of anticholinergic agents in patients with COPD may reflect increased vagal reactivity due to dysfunction of M(2) muscarinic receptors. The function of M(2) receptors and the magnitude of vagally induced bronchoconstriction were assessed in subjects with normal lung function and in subjects with COPD. A nasal cold dry air challenge was used to induce a bronchoconstriction, measured as a change in airway resistance (Raw) at 5 Hz (R5) using impulse oscillometry. In subjects with COPD R5 rose from 0.68 +/- 0.06 to 0.74 +/- 0.07 kPa/L/s after the cold dry air challenge (p < 0.01) and in the control subjects R5 rose from 0.34 +/- 0.03 to 0.39 +/- 0.03 kPa/L/s (p < 0.01). The bronchoconstriction was inhibited by pretreatment with ipratropium bromide, indicating that it was vagally mediated. In both groups of subjects pretreatment with the selective M(2) muscarinic receptor agonist pilocarpine (5 mg/ml) prevented the cold air-induced bronchoconstriction, indicating normal function of M(2) receptors. These studies indicate that M(2) muscarinic receptors are functional in subjects with stable COPD.

Lower prevalence of asthma and atopy in Turkish children living in Germany.

Ethnic origin has been reported to affect the prevalence of atopic diseases in several studies in different parts of the world. However, little is known about the prevalence of asthma and atopy in immigrants living in Europe. The objective of this study was to evaluate the prevalence of asthma and atopy in Turkish children living in Germany and to investigate the role of ethnic origin on the development of asthma and atopy in this population. In a cross-sectional survey the prevalence of physician-diagnosed asthma, atopy, skin-prick tests and bronchial hyperresponsiveness (BHR) to cold dry air challenge was assessed in 7,445 school children aged 9-11 yrs, living in Munich, south Germany. Questionnaires were distributed to the parents for self-completion and children underwent skin prick tests and cold air hyperventilation challenge. The Turkish children showed a significantly lower prevalence of asthma (5.3 versus 9.4%, p<0.05) than their German peers. Furthermore, atopy, as assessed by skin prick tests (24.7 versus 36.7%, p<0.001) and BHR (3.9 versus 7.7%, p<0.001), was less common in Turkish children. In multivariate regression models controlling for potential explanatory factors, Turkish origin still showed a significantly lower risk of developing asthma, atopic sensitization and BHR. The prevalence of childhood asthma was therefore shown to be lower in Turkish children living in Germany than in Turkey. These findings suggest that the lower prevalence of asthma and allergy in Turkish children living in Germany might be attributable to a selection bias affecting the parents of these children, as healthy individuals may have decided to come to Germany for work.

Effect of specific immunotherapy with house dust mite extract on the bronchial responsiveness of paediatric asthma patients.

Allergic asthma is common in children, and house dust mite (HDM) is an important source of perennial allergens. Bronchial hyperresponsiveness is a functional hallmark of asthma. Specific immunotherapy (SIT) with HDM extracts were shown to decrease symptoms, but its effect on bronchial responsiveness, as measured by non-pharmacological challenges, has not been evaluated. Twenty-six paediatric asthma patients allergic to HDM participated in this study. Fourteen patients received SIT with a HDM extract (Alavac, Bencard) for 2 years, and 12 served as controls. Bronchial responsiveness was assessed non-pharmacologically by cold dry air challenge (CACh) before and 3, 6, 12 and 24 months after SIT, and 12 months after termination of SIT. After 24 months, the SIT group showed a statistically significant reduction of the mean CACh-induced changes of both forced expiratory volume in one second (-21.8+/-2.7% vs. -13.7+/-2.4%; P = 0.03) and maximal expiratory flow at 25% remaining vital capacity (-48.9+/-4.9% vs. -27.9+/-6.2%; P = 0.01). In contrast, no significant changes of bronchial responsiveness were observed in the control group. In the SIT group more patients lost their bronchial hyperresponsiveness than in the control group (6/14 vs. 1/12; P<0.05). One year after terminating SIT, the treatment group showed a tendency towards returning bronchial hyperresponsiveness. These results demonstrate that during 2 years of SIT there was a reduction of bronchial hyperresponsiveness in HDM-allergic paediatric asthma patients.

Atopy, lung function and bronchial responsiveness in symptom-free paediatric asthma patients.

In adolescence, some paediatric asthma patients will become symptom-free and require no further treatment. There is little information on the atopic status, lung function and bronchial responsiveness of these patients. Symptom-free asthma patients (n=118) aged 7.7-19.2 yrs, were evaluated 1 year after termination of therapy. Bronchial asthma had previously been diagnosed on the basis of recurrent wheezing episodes. Atopic status was assessed by skin-prick testing. Baseline lung function was measured by spirometry, flow-volume curve and plethysmography. Bronchial responsiveness was assessed nonpharmacologically by cold dry air challenge. Eighty one patients had at least one positive skin test result, and the remaining 37 were defined as nonatopic. In atopic subjects, the prevalence of bronchial hyperresponsiveness was significantly higher than in nonatopic patients (41 out of 81 versus 7 out of 37; p=0.001). Atopic subjects showed a significantly lower maximal expiratory flow at 25% remaining vital capacity (p<0.05) and a higher residual volume (p<0.05) than nonatopic subjects. Nonatopic subjects were significantly younger than atopic patients (p<0.01). These symptom- and medication-free paediatric and adolescent asthma patients could, thus, be divided into two groups: 1) atopic subjects with a tendency towards bronchial hyperresponsiveness; and 2) nonatopic subjects with better lung function and normal bronchial responsiveness In view of the increased understanding of the epidemiology of early childhood wheezing, these findings support the concept of different pathogenic mechanisms underlying wheezing episodes in early childhood.

A Comparison of a Single-Step Cold-Dry Air Challenge and a Routine Histamine Provocation for the Assessment of Bronchial Responsiveness in Children and Adolescents

It has remained unclear whether bronchial responsiveness as measured by a single-step cold-dry air challenge (CACh) correlates closely to the responsiveness that is assessed by a routine pharmacologic challenge. On 2 consecutive days, we performed a CACh and a histamine challenge in 128 symptom- and medication-free pediatric and adolescent asthma patients. The CACh consisted of 4 min of isocapnic hyperventilation of -10 degrees C, absolutely dry air; responsiveness was expressed by the induced change in FEV1 (delta FEV1). The histamine challenge consisted of sequential inhalations of incremental increases in concentrations of histamine; responsiveness was expressed by the concentration which caused a 20% fall of FEV1 (PC20). Five children did not bronchoconstrict sufficiently in the histamine challenge for measuring a PC20 and were excluded from analysis. In the remaining 123, delta FEV1 (CACh) ranged from +5 to -73%, PC20 (histamine) from 0.05 to 7.2 mg/mL. There was a statistically significant correlation between delta FEV1 and PC20 (r = 0.54, p < 0.001), but also a considerable scatter of individual data points around the regression line. Fifty-two subjects were hyperresponsive by CACh and 114 by histamine criteria. There is a relatively weak correlation between the results of these two challenges; thus, one cannot be substituted one for the other. Histamine appears as more sensitive in detecting airway hyperresponsiveness than CACh. The poor correlation between the responses to these two challenges can be explained by differences between the challenge protocols, or, alternatively, by differences between applied stimuli and activated mechanisms.

Cold dry air challenge for measuring bronchial responsiveness — where do we stand?

Cold dry air challenge for measuring bronchial responsiveness — where do we stand?

Steroid-induced Reduction of Histamine Release Does Not Alter the Clinical Nasal Response to Cold, Dry Air

In some persons, cold, dry air (CDA) provokes symptoms of rhinitis that are associated with increased levels of histamine and other inflammatory mediators in nasal lavages. Because the patterns of mediators released during the early reaction to antigen and CDA-induced rhinitis are similar, we believe that mast cell activation is part of the reaction to CDA. In view of our previous finding that 1-wk pretreatment with topical steroids reduced symptoms and mediator release in the early nasal response to antigen of allergic subjects, we examined the effect of beclomethasone dipropionate on the response to CDA. Using a double-blind, crossover design, 84 micrograms of beclomethasone or placebo were administered in each nostril twice a day to 13 volunteers for 7 days prior to CDA challenge. The reaction to CDA was monitored by measuring the levels of histamine, N-alpha-p-tosyl-L-arginine methyl ester (TAME)-esterase activity and albumin in nasal lavages before and after provocation. Overall symptom scores, as well as scores for rhinorrhea and congestion, were also obtained. Cold, dry air challenge resulted in elevation over baseline of all parameters after placebo pretreatment. After beclomethasone, a significant reduction in histamine levels, but not in TAME-esterase activity or albumin levels or in number of symptoms, was observed. These results indicate that 1-wk pretreatment with beclomethasone affects mast cells, reducing histamine release after CDA, as it did in antigen-induced rhinitis. They also indicate that histamine may not be essential for the development of the immediate nasal reaction to CDA.

Nasal Challenge with Cold, Dry Air Induces a Late-Phase Reaction

Nasal challenge of susceptible persons with cold, dry air (CDA) (breathing air at a temperature of -7 to -10 degrees C and a relative humidity of 0 to 10% at a flow rate of 12.5 ml/min for 15 min) stimulates nasal symptoms and release of histamine and other mediators associated with mast-cell activation. To investigate whether such a nonantigenic stimulus induces a late-phase reaction (LPR) in the nose, we challenged 12 preselected volunteers who had previously shown an immediate response to CDA. We monitored the subjects' responses for 10 h by means of symptom diaries and the levels of histamine and TAME-esterase activity in nasal lavage fluids. All 12 subjects showed an immediate response, whereas 8 had a LPR, as indicated by a recurrence of symptoms (rhinorrhea and congestion) hours later, accompanied by an increase in the levels of histamine and TAME-esterase activity. Rhinorrhea and congestion were concomitant with the late reelevation of mediators. Control challenges of these subjects with warm, moist air (WMA), as well as serial nasal lavages without any stimulation of the nose, failed to induce an early- or a late-phase response. The amount of both mediators and symptoms generated during the 10 h after the initial reaction to CDA challenge was significantly greater (p less than 0.02) than after WMA challenge or after performance of nasal lavages without a challenge. The ability of CDA to induce a LPR strengthens the connection between initial mast-cell activation and the occurrence of a LPR.

Studies on the allergic and nonallergic nasal inflammation

Nasal lavage after antigenic and nonantigenic nasal stimulation has become an important tool for the study of inflammatory phenomena in the upper airway. Biochemical and cytologic information is relatively easily obtainable, and pharmacologic manipulations can be readily monitored. This article is of several studies aiming toward a more profound understanding of the mechanisms of allergic and nonallergic rhinitis by the use of laboratory-challenge procedures and nasal-lavage techniques. An early and a late reaction are detected clinically in the nose after antigen challenge of allergic individuals. In addition, the sensitivity to antigen significantly increases after the initial challenge, and this phenomenon is not obligatorily linked to the presence of a late-phase reaction (LPR). Inflammatory mediators, mostly mast cell- and/or basophil-derived, are detected in the nasal washes and correlate with the symptomatology in both the early and the late reactions. The allergen-induced LPR is marked by an early influx of eosinophils and, later, basophils and neutrophils. Elevation of major basic protein and histamine, but not prostaglandin D 2, is detected during the LPR, giving evidence of active eosinophil and basophil participation. Systemic steroids can effectively suppress the clinical, biochemic, and cellular manifestations of antigen-induced LPR. Topical steroids have a similar effect but are also capable of suppressing the early reaction to antigen. A nonallergic form of rhinitis can be induced in the laboratory by nasal inhalation of dry air at freezing temperatures in individuals who report sensitivity to cold and windy environments. Early and late reactions are also detectable with this stimulus, and the panel of mediators appears to be identical with that of antigen-induced rhinitis, indicating activation of the same cell type(s). This stimulus, however, appears to act through different mechanisms, since pharmacologic agents that control the allergen response are inactive against cold, dry air (CDA) reactions. Studies on the mechanism of CDA-induced rhinitis have detected elevations in the osmolality of nasal secretions after CDA challenge. This occurs only in CDA-sensitive subjects and not in CDA nonresponders or antigen-challenged allergic individuals. Elevated osmolality correlates with mediator release, suggesting a role of nasal fluid tonicity in mast cell activation. The above pieces of information offer significant insight in the mechanisms of allergic and nonallergic inflammation of the nose and the upper airways. Reconstitution of that information into a persuasive model of the naturally occurring disease and development of new therapeutic modalities will be our tasks in the future.

Airway responsiveness to cold, dry air in normal infants

Reactive airway disease may be related to genetic, infectious, and environmental factors. The latter two have been well documented, but there are no data on nonspecific airway responsiveness in normal infants prior to any insult to the respiratory tract. We measured forced expiratory flow by the thoracic compression technique and lung volume in 30 normal infants before and after challenge with cold, dry air (CDA) and compared the results with those in 12 infants who did not receive CDA challenge. As a group, infants challenged with CDA had a mean decrease in VmaxFRC of 17.9 +/- 24.1% SD. This was significantly different (P less than 0.01) from the lack of change (+ 1.3 +/- 18.1% SD) seen in the control group. We conclude that nonspecific airway reactivity may exist from early infancy and may predate any known lung injury. The relationship of this airway responsiveness to subsequent reactive airway disease and other respiratory illnesses is unknown and requires longitudinal study.