Measurements Of Airway Responsiveness Research Articles

Airway resistance: synonyms, surrogates, and precision

to the editor: The continued use of and reports on “unrestrained plethysmography” ([5][1]), which is an attractively convenient and hence popular and easy-to-misuse method of respiratory monitoring, have evoked a vigorous negative response from the respiratory physiology community. Efforts have

P5 Airway responsiveness measurements in asthmatic recruits to emergency services

Asthmatics undertaking emergency service work are thought to be at increased risk of severe bronchoconstriction with sudden exertion or exposure to irritants such as fire smoke, pepper spray or CS...

Methacholine‐induced lung function changes measured with infant body plethysmography

Several techniques have been applied to measure airway responsiveness (AR) in infants, but there are limited data on lung function changes measured by body plethysmography during induced bronchoconstriction. The aim of this study was to compare changes in maximum forced expiratory flow measured at functional residual capacity (V'(maxFRC)) by rapid thoracoabdominal compression (RTC) technique with plethysmographic measurements of specific airway conductance (sG(aw) ), and to investigate whether changes in functional residual capacity (FRC) occur during methacholine-induced bronchoconstriction in infants. We examined 94 infants with recurrent airway symptoms using methacholine airway challenge test including RTC and plethysmographic measurements. A significant association between changes in V'(maxFRC) and sG(aw) (r = 0.30; P = 0.004) was observed, but after adjustments with baseline variability the changes in V'(maxFRC) were greater and showed a closer association with changes in oxygen saturation. At the point of maximal airway obstruction, there was a poor agreement between V'(maxFRC) and sG(aw) to indicate a significant methacholine-induced bronchoconstriction. Airway challenge was also associated with a significant increase in FRC (P < 0.001), with decreasing V'(maxFRC). We conclude that in infants undergoing airway challenge with methacholine, plethysmographic measurements of sG(aw) correlate with the changes in V(maxFRC), but the agreement is poor and the methods cannot be used interchangeably. V(maxFRC) is also more sensitive to detect airway obstruction than sG(aw). However, methacholine-induced bronchoconstriction was associated with significant increases in FRC, which may affect the validity of V(maxFRC) measurements during the test.

Annexin 1-Derived Peptide Ac2-26 Inhibits Eosinophil Recruitment in vivo via Decreasing Prostaglandin D2

Background: Asthma is a chronic inflammatory disease of the mucosa and is associated with excess TH₂ cytokines, eotaxin, prostaglandin D₂ (PGD₂) and eosinophilia in the lungs. Previous studies have emphasized that the N-terminal peptide of annexin 1 (peptide Ac2-26) can inhibit mast cell degranulation, antigen-induced eotaxin release as well as the accumulation of both neutrophils and eosinophils in a model of rat pleurisy. The purpose of this study was to demonstrate anti-asthmatic effects of Ac2-26 in an asthma model and to explore possible mechanisms involved. Methods: The effect of Ac2-26 on TH₂ cytokine release, eotaxin production, PGD₂ levels and the development of pulmonary eosinophilic inflammation was compared with glucocorticoids in an asthmatic rat model. The study was conducted on rats sensitized and challenged with ovalbumin and plethysmography measured airway responsiveness. Bronchoalveolar lavage (BAL) histopathology and the levels of cytokines, chemokines as well as PGD₂ were examined. Results: Our results showed that Ac2-26 suppressed the accumulation of eosinophils in airways, reduced IL-4, IL-5, IL-13, PGD₂ and eotaxin levels in the BAL fluid, and lowered the expression of CRTH2. Exogenous PGD₂ significantly attenuated the biological effects of Ac2-26. Conclusion: These results indicated that Ac2-26 exerted broad inhibitory effects on airway inflammation and hyperresponsiveness in a rat model of asthma. Exogenous PGD₂ reversed the inhibitory effects of AC2-26 on eosinophil recruitment. Ac2-26 exhibited anti-asthmatic, immunomodulatory activity that was substantially mediated by decreasing PGD₂ production and its CRTH2 receptor expression in vivo.

Recognition and surveillance of occupational asthma: a preventable illness with missed opportunities

Occupational asthma is common, disabling and costly, and it is often difficult to diagnose. Incidence statistics are consequently unreliable, and there are formidable difficulties in recognizing and managing what should be a preventable illness. The opportunities have largely been missed. The author offers a personal view of what, ideally, should be done--recognizing that at present the ideal is not readily practical. Always consider the possibility of an occupational cause at the time adult-onset asthma is first recognized-the probability of this is of the order 9-15%. Do not prescribe treatment unless this possibility is remote or the asthma is life-threatening. If the possibility is not remote seek immediate advice from a specialized centre, without prescribing masking medication and without curtailing usual work practice. The specialized referral centre should place the accurate measurement of airway responsiveness at the centre of investigatory strategies. A return-to-work study, monitored by serial measurements of airway responsiveness and ventilatory function, provides adequate objective evidence for diagnosis in most cases. When a novel cause is suspected, specific inhalation provocation testing with the particular agent in the specialized centre is desirable. Regular competent surveillance is necessary in high-risk occupational environments; this should include environmental monitoring, the detection of relevant new symptoms, spirometry measurements, serum antibody studies (where available) and a robust protocol for managing inevitable failed attendances.

Experimental hookworm infection: a randomized placebo‐controlled trial in asthma

BackgroundEpidemiological studies suggest that hookworm infection protects against asthma, and therefore that hookworm infection may have a direct or an indirect therapeutic potential in this disease. We now report the first clinical trial of experimental hookworm infection in people with allergic asthma.ObjectivesTo determine the effects of experimental hookworm infection in asthma.MethodsThirty-two individuals with asthma and measurable airway responsiveness to adenosine monophosphate (AMP) were randomized and double blinded to cutaneous administration of either ten Necator americanus larvae, or histamine solution (placebo), and followed for 16 weeks. The primary outcome was the change in provocation dose of inhaled AMP required to reduce forced expiratory volume in 1 s by 20% (PD20AMP) from baseline to week 16. Secondary outcomes included change in several measures of asthma control and allergen skin sensitivity and the occurrence of adverse effects.ResultsMean PD20AMP improved in both groups, more in the hookworm [1.49 doubling doses (DD)] than the placebo group (0.98 DD), but the difference between groups was not significant (0.51 DD; 95% confidence interval: −1.79 to 2.80; P=0.65). There were no significant differences between the two groups for other measures of asthma control or allergen skin sensitization. Infection was generally well tolerated.ConclusionsExperimental infection with ten hookworm larvae in asthma did not result in significant improvement in bronchial responsiveness or other measures of asthma control in this study. However, infection was well tolerated and resulted in a non-significant improvement in airway responsiveness, indicating that further studies that mimic more closely natural infection are feasible and should be undertaken.Cite this as: J. R. Feary, A. J. Venn, K. Mortimer, A. P Brown, D. Hooi, F. H. Falcone, D. I. Pritchard and J. R. Britton, Clinical & Experimental Allergy, 2010 (40) 299– 306.

Diagnostic properties of inhaled mannitol in the diagnosis of asthma: A population study

A new indirect bronchial provocation test measuring airway responsiveness by using inhaled mannitol was recently introduced. The aim of this study was to examine the diagnostic properties of airway responsiveness to inhaled mannitol in the assessment of asthma in an unselected sample of young adults. Two hundred thirty-eight young adults randomly drawn from the nationwide civil registration list were challenged with inhaled, dry-powder mannitol. A respiratory specialist, blind to the test results, classified all 238 subjects with respect to the presence of asthma. The classification was based on respiratory symptoms, spirometric results, atopy, and fraction of exhaled nitric oxide values and response to inhaled beta(2)-agonists. On this basis, sensitivity, specificity, and predictive values were assessed to different cutoff values of the test. A receiver operating characteristic curve was constructed, and the accuracy of the test, defined as the area under the curve, was computed. Fifty-one (21.4%) subjects had current asthma. Of 33 subjects with airway hyperresponsiveness to mannitol, 30 had current asthma. The specificity and sensitivity were 98.4% (95% CI, 96.2% to 99.4%) and 58.8% (95% CI, 50.7% to 62.6%), respectively. The positive predictive value (PPV) and negative predictive value (NPV) were 90.9% (95% CI, 78.4% to 96.8%) and 89.8 (95% CI, 87.7% to 90.7%), respectively. The area under the receiver operating characteristic curve was 0.89 (95% CI, 0.83-0.95). In an unselected sample of young adults, bronchial provocation with inhaled dry-powder mannitol had a high diagnostic specificity for the diagnosis of asthma.

Methacholine challenge – Comparison of an ATS protocol to a new rapid single concentration technique

Bronchial methacholine challenge is well established in asthma diagnostics and research. ATS guidelines propose a five step standard dosimeter (SDM) protocol with incremental concentrations of methacholine to calculate the concentration causing a 20% drop in FEV(1) in an individual (PC(20)FEV(1)). In contrast, the aerosol provocation system (APS) by Viasys automatically determines the administered dose of methacholine by measuring the effective nebulisation time and referring it to drug concentration and nebuliser power. Therefore, it offers a feasible and less time-consuming provocation procedure by applying incremental doses (PD(20)) of methacholine using a single concentration (16mg/mL methacholine, APS-SC). In this study we compared these two methods in 52 young adults (25+/-5.8 years). Following a screening visit, subjects were randomly assigned to undergo either SDM or APS-SC followed by the other method within 1 week. A close correlation between concentration and dosage causing a 20% fall of FEV(1) was found (r=0.69, p<0.001). Using the ATS categorisation of bronchial responsiveness we interpreted the results of the APS-SC method as follows: PD(20) methacholine<0.3mg as "moderate to severe BHR", 0.3 - 0.6mg as "mild BHR", 0.6 - 1.0mg as "borderline BHR", and>1.0mg as "normal bronchial response". We conclude that the five-step APS-SC is a suitable method, providing reliable results. In clinical practice the APS-SC is a timesaving procedure and less prone to errors since only one dilution of methacholine is necessary compared to the SDM.

Does unrestrained single-chamber plethysmography provide a valid assessment of airway responsiveness in allergic BALB/c mice?

BackgroundUnrestrained plethysmography has been used to monitor bronchoconstriction because of its ease of use and ability to measure airway responsiveness in conscious animals. However, its reliability remains controversial.ObjectiveTo investigate if unrestrained plethysmography could provide a valid interpretation of airway responsiveness in allergic BALB/c mice.MethodsOvalbumin sensitized BALB/c mice were randomized to receive either a single-dose Ovalbumin challenge (OVA-1D group) or a three-dose Ovalbumin challenge (OVA-3D group). The OVA-1D group was further divided into OVA-1D-I (measured invasively, using lung resistance as the index of responsiveness) and OVA-1D-N group (measured non-invasively, using Penh as the index of responsiveness). Similarly the OVA-3D group was divided into OVA-3D-I and OVA-3D-N groups based on the above methods. The control groups were sensitized and challenged with normal saline. Bronchial alveolar lavage fluid was taken and airway histopathology was evaluated for airway inflammation. Nasal responsiveness was tested with histamine challenge.ResultsCompared with controls, a significant increase in airway responsiveness was shown in the OVA-1D-N group (P < 0.05) but not in the OVA-1D-I group. Both OVA-3D-I and OVA-3D-N groups showed higher responsiveness than their controls (P < 0.05). The nasal mucosa was infiltrated by eosinophic cells in all Ovalbumin immunized groups. Sneezing or nasal rubbing in allergic groups appeared more frequent than that in the control groups.ConclusionPenh can not be used as a surrogate for airway resistance. The invasive measurement is specific to lower airway. Penh measurement (done as a screening procedure), must be confirmed by a direct invasive measurement specific to lower airway in evaluating lower airway responsiveness.

Safety of hookworm infection in individuals with measurable airway responsiveness: a randomized placebo‐controlled feasibility study

BackgroundEpidemiological evidence suggests that hookworm infection protects against asthma. However, for ethical and safety reasons, before testing this hypothesis in a clinical trial in asthma it is necessary to establish whether experimental hookworm infection might exacerbate airway responsiveness during larval lung migration.ObjectiveTo determine whether hookworm larval migration through the lungs increases airway responsiveness in allergic individuals with measurable airway responsiveness but not clinical asthma, and investigate the general tolerability of infection and effect on allergic symptoms.MethodsThirty individuals with allergic rhinoconjunctivitis and measurable airway responsiveness to adenosine monophosphate (AMP) but not clinically diagnosed asthma were randomized, double-blind to cutaneous administration of either 10 hookworm larvae or histamine placebo, and followed for 12 weeks. The primary outcome was the maximum fall from baseline in provocative dose of inhaled AMP required to reduce 1-s forced expiratory volume by 10% (PD10AMP) measured at any time over the 4 weeks after active or placebo infection. Secondary outcomes included peak flow variability in the 4 weeks after infection, rhinoconjunctivitis symptom severity and adverse effect diary scores over the 12-week study period, and change in allergen skin test responses between baseline and 12 weeks.ResultsMean maximum change in PD10AMP from baseline was slightly but not significantly greater in the hookworm than the placebo group (−1.67 and −1.16 doubling doses; mean difference −0.51, 95% confidence interval −1.80 to 0.78, P=0.42). Symptom scores of potential adverse effects were more commonly reported in the hookworm group, but infection was generally well tolerated. There were no significant differences in peak-flow variability, rhinoconjunctivitis symptoms or skin test responses between groups.ConclusionHookworm infection did not cause clinically significant exacerbation of airway responsiveness and was well tolerated. Suitably powered trials are now indicated to determine the clinical effectiveness of hookworm infection in allergic rhinoconjunctivitis and asthma.

Reproducibility of Airway Responsiveness in Horses Using Flowmetric Plethysmography and Histamine Bronchoprovocation

Inflammatory airway disease has a high prevalence in horses, but is often a diagnostic challenge. Flowmetric plethysmography and histamine bronchoprovocation (FP/HBP) is a simple and effective tool for diagnosis, but reproducibility of these measurements made over time has not been established. We hypothesize that the measurement of airway responsiveness in horses using FP/HBP is consistent over both short and long periods of time. Twenty-nine healthy adult horses from 2 university herds. In this prospective experimental study, airway responsiveness was determined in each horse at day 0 (baseline [BL]) with FP/ HBP, using PC35 (provocative concentration of histamine needed to increase Delta(flow) by 35%) as a measure of airway responsiveness. Each horse was re-tested 1-4 weeks after BL (short-term [ST]) and again at 3-12 months after BL (long-term [LT]). In the ST period, 23/27 (85%) of the horses had a PC35 that was within 1 doubling concentration of histamine of their BL value, with a mean change of 0.52 doubling concentrations (95% CI 0.26-0.79, range 0-2.06). For the LT data, 19/26 (73%) of horses were within 1 doubling concentration of their BL value, with a mean change of 0.81 doubling concentrations (95% CI 0.45-1.17, range 0.14-3.10). There was no significant difference in reproducibility between the 2 groups of subjects. Repeated measurements of airway responsiveness obtained with FP/HBP show acceptable reproducibility over time periods up to a year. However, caution must be used when testing horses when ambient air temperature is low.

Effect of the inhaled corticosteroid mometasone on small airway patency in patients with asthma

The inflammation in asthma involves both the large and the small airways. This study was designed to examine whether mometasone delivered from a dry powder inhaler would improve those parameters thought to reflect patency and obstruction of the small airways (diameter <2 mm). Subjects with mild to moderate asthma, only receiving short-acting beta-agonists, underwent baseline assessment, and then were randomized to receive for 12 weeks either mometasone 400 micrograms once daily in the evening or matching placebo. Outcomes assessed included clinical measures and measures of airway responsiveness and inflammation included methacholine sensitivity (concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second [FEV(1)] [PC(20)]), exhaled nitric oxide, serum ECP, and sputum eosinophils. Pulmonary function was assessed by spirometry, plethysmography, and forced oscillometry. Measures of small airway patency included single breath nitrogen washout and air trapping on expiratory high-resolution computed tomography. Results were available on 12 adult subjects who received mometasone and 14 subjects who received placebo. Among tests reflecting small airway patency, the forced expiratory flow between 25 and 75% of vital capacity was significantly improved by mometasone compared with placebo (+9% versus -6%; p = 0.006 and the closing volume over forced vital capacity (FVC; -2% versus 0%; p = 0.05). Other results significantly favoring mometasone over placebo included FEV(1), FVC, PC(20), and A.M. and P.M. peak expiratory flows, and albuterol use. Mometasone delivered by a dry powder inhaler improved asthma control and pulmonary function in tests reflecting both large and small airways.

Bronchodilator effect of deep inspiration and bronchoconstriction-triggered cough

BackgroundCough in the patients with cough variant asthma is triggered by bronchoconstriction, which responds to bronchodilator therapy. Following airway narrowing induced by inhaled methacholine, deep inspiration (DI) causes dilation of the airways in both asthmatic and non-asthmatic subjects. The aim of the present study was to investigate the relationship between bronchodilator effect of DI and bronchoconstriction-triggered cough.MethodsWe measured airway responsiveness to methacholine using partial and full flow-volume curves in 28 healthy adults. The expiratory flow at 40% above residual volume from the full forced vital capacity (MEF40) was obtained and the volume was used as the reference volume to determine the isovolume flow from the partial curve (PEF40). Coughs were counted for 32 min during and following the inhalation of methacholine at the provocative concentration which produced a 20% fall or more in FEV1from the post-saline value (PC20-FEV1). The bronchodilator effect of DI on bronchoconstriction induced by methacholine at the PC20-FEV1 concentration was expressed as the ratio of (MEF40-PEF40)/PEF40 (DI index).ResultsThe number of coughs for 32 min during and following the inhalation of PC20-FEV1 concentration of methacholine was 39.3 ± 29.7 (mean ± SD)/32 min. The number of coughs during and following the inhalation was correlated with DI index (r = 0.57, p = 0.0015), but not with PC20-FEV1 or change in FEV1 or PEF40 by inhalation of the PC20-FEV1 concentration of methacholine.ConclusionWe found that methacholine-induced cough was associated with the bronchodilator effect of DI on methacholine induced-bronchoconstriction in normal subjects.

Survey of airborne pollen in Hubei province of China

To study the genera and seasonal distribution of airborne pollen in Hubei province of China, and its relationship with pollinosis. From November 2003 to October 2004, an airborne pollen investigation was performed in 16 chosen areas in 12 cities of Hubei province using gravity sedimentation technique. Meanwhile, univalent skin prick tests of pollens were performed and the invasion season was studied on 2,300 patients with pollinosis. Among them, 352 cases underwent the airway responsiveness measurements, and the correlation between airway responsiveness and results of pollen count was analyzed. A total of 61 pollen genera were observed and 257,520 pollens were collected. The peak of airborne pollen distribution occurred in two seasons each year: spring (March and April) and autumn (from August to October). The attack of pollinosis corresponded to the peak of pollen distribution. There was a significantly negative relationship between the provocation dose causing a 20% decrease of forced expiratory volume in one second (FEV1) from baseline and airborne pollen concentration (r= -0.6829, P < 0.05). This study provides useful information for airborne pollen epidemiology of Hubei province, and it provides important insights to clinical prevention, diagnosis, and treatment of pollen-related allergic diseases.

Differences in the Response to Methacholine Between the Tidal Breathing and Dosimeter Methods: Influence of the Dose of Bronchoconstrictor Agent Delivered to the Mouth

Background It has been postulated that differences in provocative concentration of methacholine causing a 20% fall in FEV 1 (PC 20 ) values between the dosimeter method and tidal breathing method might be due to differences in the dose of agonist delivered to the mouth. The aim of the present study was to determine the influence of the dose of aerosol delivered to the mouth on differences in the response obtained with each challenge method. Methods This study measured airway responsiveness to methacholine by dosimeter method and tidal breathing method in 27 subjects with suspected asthma. The dosimeter was modified to deliver an identical volume to that obtained with the tidal breathing method. Concentration-response curves were characterized by the PC 20 . Results The dosimeter method PC 20 was significantly higher than the tidal breathing method PC 20 , with geometric mean values of 4.03 (95% confidence interval [CI], 1.86 to 8.78 mg/mL) and 2.19 (95% CI, 1.32 to 3.64 mg/mL; p=0.04), respectively. The mean difference in the PC 20 value detected with each method was similar in subjects with tidal breathing method PC 20 values ≥ 2 mg/mL (0.77 doubling concentrations) and in those with PC 20 values Conclusions The tidal breathing method produces PC 20 values significantly lower than a modified dosimeter method, which delivers the same volume of aerosol. These results suggest that the discordant PC 20 values obtained with the two methods are not due to differences in the dose of agonist delivered to the mouth.

No effect of metformin on the innate airway hyperresponsiveness and increased responses to ozone observed in obese mice

We have previously reported that obese db/db mice exhibit innate airway hyperresponsiveness. These mice also have enhanced inflammatory responses to ozone, a common air pollutant that exacerbates asthma. Since db/db mice are diabetic as well as obese, the purpose of the present study was to determine whether metformin, an antihyperglycemic agent, alters the pulmonary phenotype of db/db mice. Lean wild-type (C57BL/6J) and obese db/db mice were treated by gavage with water or metformin (300 microg/g) once a day for 2 wk. Twenty-four hours after the last treatment, in mice of both genotypes, we either measured airway responsiveness to methacholine by forced oscillation, or we exposed the mice to ozone (2 parts per million for 3 h) and examined the ensuing inflammatory response. Compared with water, treatment with metformin caused a significant decrease in fasting blood glucose in obese mice. Airway responsiveness was increased in db/db versus wild-type mice, but metformin did not affect responsiveness in either group. Four hours after exposure to ozone, there was a significant increase in bronchoalveolar lavage fluid neutrophils and chemokines in mice of both genotypes, but the magnitude of these changes was greater in db/db than wild-type mice. Metformin did not affect ozone-induced inflammation in mice of either genotype. The results indicate that hyperglycemia is unlikely to account for the pulmonary phenotype of obese mice.

Invasive and noninvasive methods for studying pulmonary function in mice

The widespread use of genetically altered mouse models of experimental asthma has stimulated the development of lung function techniques in vivo to characterize the functional results of genetic manipulations. Here, we describe various classical and recent methods of measuring airway responsiveness in vivo including both invasive methodologies in anesthetized, intubated mice (repetitive/non-repetitive assessment of pulmonary resistance (RL) and dynamic compliance (Cdyn); measurement of low-frequency forced oscillations (LFOT)) and noninvasive technologies in conscious animals (head-out body plethysmography; barometric whole-body plethysmography). Outlined are the technical principles, validation and applications as well as the strengths and weaknesses of each methodology. Reviewed is the current set of invasive and noninvasive methods of measuring murine pulmonary function, with particular emphasis on practical considerations that should be considered when applying them for phenotyping in the laboratory mouse.

Activation of protease‐activated receptor‐2 reduces airways inflammation in experimental allergic asthma

Proteinase-activated receptors (PAR)-2 are members of the family of G-protein-coupled receptors activated by proteases. These receptors are widely expressed in several tissues and in virtually all cells involved in rhinitis and asthma. In particular, proteinases activating PAR-2 may affect airway functions and play a role in human diseases. Assessment of the role of PAR-2 in bronchoconstriction, airway responsiveness and immune response after allergic challenge, in rabbits sensitized to Par j 1, the major allergen of Parietaria judaica pollen. Evaluation of antigen challenge in rabbits treated with PAR-2-activating peptide (PAR-2AP) (SLIGRL) or the scrambled peptide LSIGRL or vehicle immediately before allergen exposure measuring airway responsiveness. Characterization of bronchoalveolar lavage (BAL) following histamine challenge and phenotype analysis of cells by flow cytometry and analysis of cytokine production by quantitative PCR. PAR-2AP pre-treatment, but not the scrambled peptide, was able to significantly inhibit bronchoconstriction, airway hyper-responsiveness and to modulate the immune response induced by allergic challenge in sensitized rabbits. The phenotype analysis of the cells recovered from BAL showed an increase in RLA-DR-positive cells while RTLA-positive cells were unchanged. IFN-gamma and IL-2 production were inhibited, with a concomitant increase in IL-10 of about 10-fold over the control values. In this experimental model, PAR-2 modulates bronchoconstriction interfering with antigen challenge-induced immune response in rabbits sensitized and challenged to Par j 1.

Reply to Agrawal and Ram

Reply : We appreciate the thoughtful comments from A. Agrawal and A. Ram in their adjoining letter concerning 1 ) typos in the text (which have now been addressed by issuance by the Journal of a corrigendum), and 2 ) various aspects of originality and accuracy to measure specific airway resistance (

Arhgef1 Is Required by T Cells for the Development of Airway Hyperreactivity and Inflammation

Arhgef1 is an intracellular protein, expressed by hematopoietic cells, that regulates signaling by both G protein-coupled receptors and RhoA, and, consequently, is required for appropriate migration and adhesion of diverse leukocyte populations. To evaluate a possible contribution for Arhgef1 in the development of airway inflammation and airway hyperreactivity. Arhgef1-deficient (Arhgef1-/-) and wild-type (WT) mice were sensitized and airway challenged, followed by measurement of airway responsiveness to inhaled methacholine. Inflammation was assessed by several parameters that included flow cytometric analysis and histology. Arhgef1-deficient recipients were reconstituted with WT T lymphocytes before sensitization and challenge, and again measured for airway responsiveness and inflammation. Cytokine production in response to specific antigen was measured in cultures of isolated leukocytes from lung and spleen and compared with the levels generated in lung and spleen explant cultures. Arhgef1-/- mice display significantly reduced airway hyperreactivity, Th2 cytokine production, and lung inflammation, despite intact systemic immunity. After airway challenge of Arhgef1-/- mice, antigen-specific T cells were present in mutant lungs, but were found to interact with CD11c+ cells at a significantly reduced frequency. Adoptive transfer of WT T cells into Arhgef1-/- mice restored airway hyperreactivity and inflammation. These data demonstrate that T cells depend on Arhgef1 to promote lung inflammation. Moreover, a deficiency in Arhgef1 results in reduced T cell-CD11c+ antigen-presenting cell interaction, and likely underscores the inability of Arhgef1-/- mice to mount an adaptive immune response to airway challenge.