Histamine Bronchoprovocation Research Articles

Flow interruption compared to forced oscillatory maneuvers and esophageal balloon/pneumotachography for measurement of respiratory resistance in the horse.

Pulmonary function testing is critical to the diagnosis of equine asthma (EA), an important cause of respiratory disease in the horse, but its clinical use has remained elusive, unfortunately, due to the complexity of reference methods, esophageal balloon/pneumotachography (EBP), and forced oscillatory mechanics (FOM), so we sought a noninvasive, portable method for use in horses through rapid interruption of airflow for equilibration of alveolar pressure with proximal airway pressure, termed flow interruption (FI). Resistance (RINT) was computed as the relationship between the change in pressure at the nose before and immediately after interruption and flow immediately before interruption. A pilot study in five healthy university-owned animals using EBP and FI showed good correspondence between the two methods: RINT (0.33 ± 0.05 cmH2O/L/s) and RL (0.31 ± 0.06 cmH2O/L/s). In two separate populations of client-owned horses, with random assignment of methods to FI versus EBP (n = 8), RINT showed good correlation with RL in horses (rs = 0.995, P = 0.0002) and accords with RL, with no significant difference between RINT and RL. Using FOM (n = 12), RINT (0.67 ± 0.31 cmH2O/L/s) has good correlation with RRS measured with FOM (r = 0.834, P = 0.0001), but is consistently smaller than RRS (0.74 ± 0.33 cmH2O/L/s). Histamine bronchoprovocation (HBP) was performed in a subset of these horses: FI classified one horse in six as less reactive than did EBP, and FI classified one horse in seven as less reactive than did FOM.NEW & NOTEWORTHY We developed and document for the first time the use of flow interruption for the rapid and noninvasive measurement of resistance in equine patients and demonstrated short- and long-term stability and accuracy in comparison with the reference methods.

Clinical effects and pharmacokinetics of nebulized lidocaine in healthy horses.

BackgroundNebulized lidocaine appears promising as a novel corticosteroid-sparing therapeutic for equine asthma, but its safety and pharmacokinetic behavior have yet to be confirmed.ObjectiveTo describe the effect of nebulized lidocaine on upper airway sensitivity, lung mechanics, and lower respiratory cellular response of healthy horses, as well as delivery of lidocaine to lower airways, and its subsequent absorption, clearance, and duration of detectability.AnimalsSix healthy university- and client-owned horses with normal physical examination and serum amyloid A, and no history of respiratory disease within 6 months.MethodsProspective, descriptive study evaluating the immediate effects of 1 mg/kg 4% preservative-free lidocaine following nebulization with the Flexineb®. Prior to and following nebulization, horses were assessed using upper airway endoscopy, bronchoalveolar lavage, and pulmonary function testing with esophageal balloon/pneumotachography and histamine bronchoprovocation. Additionally, blood and urine were collected at predetermined times following single-dose intravenous and nebulized lidocaine administration for pharmacokinetic analysis.ResultsUpper airway sensitivity was unchanged following lidocaine nebulization, and no laryngospasm or excessive salivation was noted. Lidocaine nebulization (1 mg/kg) resulted in a mean epithelial lining fluid concentration of 9.63 ± 5.05 μg/mL, and a bioavailability of 29.7 ± 7.76%. Lidocaine concentrations were higher in epithelial lining fluid than in systemic circulation (Cmax 149.23 ± 78.74 μg/L, CELF:Cmaxplasma 64.4, range 26.5–136.8). Serum and urine lidocaine levels remained detectable for 24 and 48 h, respectively, following nebulization of a single dose. Baseline spirometry, lung resistance and dynamic compliance, remained normal following lidocaine nebulization, with resistance decreasing post-nebulization. Compared to the pre-nebulization group, two additional horses were hyperresponsive following lidocaine nebulization. There was a significant increase in mean airway responsiveness post-lidocaine nebulization, based on lung resistance, but not dynamic compliance. One horse had BAL cytology consistent with airway inflammation both before and after lidocaine treatment.ConclusionsNebulized lidocaine was not associated with adverse effects on upper airway sensitivity or BAL cytology. While baseline lung resistance was unchanged, increased airway reactivity to histamine bronchoprovocation in the absence of clinical signs was seen in some horses following nebulization. Further research is necessary to evaluate drug delivery, adverse events, and efficacy in asthmatic horses.

Can bronchoconstriction and bronchodilatation in horses be detected using electrical impedance tomography?

BackgroundElectrical impedance tomography (EIT) generates images of the lungs based on impedance change and was able to detect changes in airflow after histamine challenge in horses.ObjectivesTo confirm that EIT can detect histamine‐provoked changes in airflow and subsequent drug‐induced bronchodilatation. Novel EIT flow variables were developed and examined for changes in airflow.MethodsBronchoconstriction was induced using stepwise histamine bronchoprovocation in 17 healthy sedated horses. The EIT variables were recorded at baseline, after saline nebulization (control), at the histamine concentration causing bronchoconstriction (Cmax) and 2 and 10 minutes after albuterol (salbutamol) administration. Peak global inspiratory (PIFEIT) and peak expiratory EIT (PEFEIT) flow, slope of the global expiratory flow‐volume curve (FVslope), steepest FVslope over all pixels in the lung field, total impedance change (surrogate for tidal volume; VTEIT) and intercept on the expiratory FV curve normalized to VTEIT (FVintercept/VTEIT) were indexed to baseline and analyzed for a difference from the control, at Cmax, 2 and 10 minutes after albuterol. Multiple linear regression explored the explanation of the variance of Δflow, a validated variable to evaluate bronchoconstriction using all EIT variables.ResultsAt Cmax, PIFEIT, PEFEIT, and FVslope significantly increased whereas FVintercept/VT decreased. All variables returned to baseline 10 minutes after albuterol. The VTEIT did not change. Multivariable investigation suggested 51% of Δflow variance was explained by a combination of PIFEIT and PEFEIT.Conclusions and Clinical ImportanceChanges in airflow during histamine challenge and subsequent albuterol administration could be detected by various EIT flow volume variables.

Comparison of Flowmetric Plethysmography and Forced Oscillatory Mechanics to Measure Airway Hyperresponsiveness in Horses.

Airway hyperresponsiveness (AHR) is linked to airway inflammation and is considered a key manifestation of mild/moderate equine asthma (EA). The study purpose was to determine whether two modalities of non-invasive lung function testing (FOM—forced oscillatory mechanics vs. FP—flowmetric plethysmography) establish the same clinical diagnosis of AHR in horses, using histamine bronchoprovocation. Nineteen horses (3–25 years, 335–650 kg) with clinical signs suggestive of mild/moderate equine asthma were enrolled. FOM and FP testing was performed in each horse on two consecutive days, using a randomized cross-over design. AHR was defined by the histamine dose needed to double FOM baseline resistance, or to achieve a 35% increase in FP delta flow. Bronchoalveolar lavage fluid (BALF) was subsequently collected and stained with modified Wright's and toluidine blue stains. Binary statistical tests (related samples T-test, Mann-Whitney U, Chi-square analyses) were performed to compare study groups, with P < 0.05 considered significant. Abnormal BALF cytology confirmed EA in 14/19 (73.7%) horses. Both FOM and FP revealed AHR in 7/14 (50%) of these EA horses. An additional 4/19 (21.1%) horses showed AHR based on FP but not FOM, including two horses with normal BALF cytology. A diagnosis of AHR was more often associated with FP than FOM (P = 0.013), although the prevalence of AHR was significantly higher in EA vs. non-EA horses, regardless of testing methodology. The phase angle between thoracic and abdominal components of breathing did not differ between test groups. In conclusion, FP diagnosed AHR more frequently than did FOM, including horses with no other diagnostic evidence of EA. Without further evaluation, these two testing modalities of AHR cannot be used interchangeably.

Bronchoalveolar lavage fluid cytology and airway hyper-reactivity in clinically normal horses.

To characterise the relationship between bronchoalveolar lavage fluid (BALF) cytology and pulmonary function testing with histamine bronchoprovocation (HBP) methods in a population of clinically normal horses. Cross-sectional study METHODS: Clinically normal adult horses (n = 33) underwent pulmonary function testing and HBP with a commercial flowmetric plethysmography system. BAL was performed 1-5 days later. Statistical analysis was used to assess associations between BALF cell concentration, relative inflammatory cell percentages and categorisation, and airway hyper-reactivity (AHR). AHR (PC35 ≤ 8 mg/mL) was demonstrated in 17 (52%) of the horses. Using current definitions, BALF cytology was consistent with inflammatory airway disease in 14 (42%) of the horses and 7 of those demonstrated either mastocytic and/or eosinophilic responses. There was no correlation between total inflammatory cell counts or relative percentage and AHR. No statistical association was found between BALF inflammatory cell categories and AHR. A direct association between cytological evidence of airway inflammation and AHR was not identified in this population of clinically normal horses. Determining the presence and measuring inflammatory cell mediators in BALF may more accurately reflect AHR. In addition, normal values for cell proportions in BALF may vary between different populations of horses and more appropriate regional reference ranges should be established.

Aggravation of airway inflammation and hyper‐responsiveness following nasal challenge with Dermatophagoides pteronyssinus in perennial allergic rhinitis without symptoms of asthma

House dust mites are the most prevalent allergen causing sensitizations in patients with rhinitis and asthma in China. We aimed to investigate the changes in both upper and lower airway inflammation and responsiveness following Dermatophagoides pteronyssinus (Der-p) nasal provocation test (NPT) in rhinitis patients. Study subjects included 15 nonasthmatic Der-p-sensitized rhinitis (AR) patients with airway hyper-responsiveness (AHR) (AR+AHR+), 15 AR patients without AHR (AR+AHR-), 15 healthy controls (HCs) with Der-p sensitization (HC+DP+), and 15 HC without Der-p sensitization (HC+DP-). All subjects underwent Der-p NPT. Visual analogue scale (VAS) scores of nasal symptoms, nasal lavage and nasal airway resistance (NAR) measurement, sputum induction, and forced expiratory volume in 1 second (FEV1 ) were performed. Airway responsiveness to histamine bronchoprovocation (PD20 -FEV1 ) and exhaled nitric oxide (FeNO) was determined. NAR increased significantly in all subjects with the greatest effect seen in AR+AHR+ individuals. VAS increased in all subjects at 30 min and returned to baseline at 6 h, with significantly higher levels in AR+AHR+ and AR+AHR- subjects (P < 0.05). Eosinophils in nasal lavage fluid and sputum increased significantly after NPT in AR+AHR+ and AR+AHR- subjects (P < 0.001). FEV1 % and PD20 -FEV1 decreased and FeNO increased significantly after NPT only in AR+AHR+ subjects (P < 0.05). Nasal lavage eosinophil count was positively correlated with sputum eosinophil count and the level of FeNO and negatively correlated with FEV1 and PD20 . House dust mite nasal provocation test induces and aggravates both upper and lower airway inflammation and hyper-responsiveness in patients with persistent allergic rhinitis without asthmatic symptoms.

Relationships between equine airway reactivity measured byflowmetric plethysmography and specific indicators of airway inflammation in horses with suspected inflammatory airway disease.

Agreement between airway reactivity measured by flowmetric plethysmography and histamine bronchoprovocation, and lower airway inflammation measured by bronchoalveolar lavage (BAL) cytology, has not been studied in horses with suspected inflammatory airway disease (IAD). We tested the hypothesis that airway reactivity is associated with BAL cytology in horses presenting for unexplained poor performance and/or chronic cough. Prospective clinical study. Forty-five horses, predominantly young Standardbred racehorses, presenting for unexplained poor performance or chronic cough, underwent endoscopic evaluation, tracheal wash, flowmetric plethysmography with histamine bronchoprovocation and BAL. Histamine response was measured by calculating PC35, the concentration of nebulised histamine eliciting an increase in Δflow of 35%. In this population, there was no significant correlation between histamine response and cell populations in BAL cytology. When airway hyperreactivity (AHR) was defined as ≥35% increase in Δflow at a histamine concentration of <6mg/ml, 24 of the 45 horses (53%) were determined to have AHR. Thirty-three (73%) had either abnormal BAL cytology or AHR, and were diagnosed with IAD on this basis. Of horses diagnosed with IAD, 9 (27%) had an abnormal BAL, 11 (33%) had AHR and 13 (39%) had both. Airway reactivity and BAL cytology did not show concordance in this population of horses presenting for unexplained poor performance and/or chronic cough. Failure to include tests of airway reactivity may lead to underdiagnosis of IAD in young Standardbred racehorses that present with clinical signs suggestive of IAD.

Age Effects on Blood Gas, Spirometry, Airway Reactivity, and Bronchoalveolar Lavage Fluid Cytology in Clinically Healthy Horses

BackgroundDespite the increasing number of geriatric horses attended by veterinarians, there is a lack of understanding of aging‐related changes on the respiratory system of horses.ObjectiveTo identify aging‐related changes on the respiratory function and bronchoalveolar lavage fluid (BALF) cytology of horses.AnimalsFifteen healthy young adult (2–11 years) and 16 healthy aged (≥20 years) horses.MethodsThe respiratory system was examined by measurement of arterial blood gases (ABG), use of respiratory inductive plethysmography (RIP) for assessment of breathing pattern and ventilatory parameters, histamine bronchoprovocation, and BALF cytology.ResultsNo significant differences were detected with regard to values obtained by ABG or bronchoprovocation of young adult and aged healthy horses. In aged horses, there were significant differences in mean ± SD of the following parameters when compared to young horses: prolonged expiratory time (Te) measured by RIP (3.9 ± 1.5 s versus 3.0 ± 0.6 s), decreased percentage of alveolar macrophages (40.6 ± 11.3% versus 53.5 ± 9.6%), and increased percentage of lymphocytes (53.4 ± 9.5% versus 43.9 ± 11.0%). No correlations between airway reactivity and ventilatory parameters, ABG, or BALF cytology were found in this asymptomatic population.ConclusionsThese results suggest that aging does not cause changes in the results obtained by ABG, most RIP‐derived variables, and bronchoprovocation in the horse. A decreased percentage of macrophage and an increased percentage of lymphocytes in the BALF cytology may be expected in the asymptomatic geriatric horse and may be a result of aging.

Effect of prolonged administration of clenbuterol on airway reactivity and sweating in horses with inflammatory airway disease

To determine whether prolonged administration of clenbuterol results in tachyphylaxis, specifically regarding its bronchoprotective properties and effect on sweating in horses. 8 Thoroughbreds with inflammatory airway disease. In a crossover design, horses received clenbuterol (0.8 μg/kg, p.o., q 12 h) or placebo for 21 days, with a washout period of ≥ 30 days between the 2 treatments. Airway reactivity was evaluated by use of flowmetric plethysmography and histamine broncho-provocation before (day 0; baseline) and every 7 days after the start of treatment. Sweat function was evaluated via response to epinephrine administered ID before and every 10 days after the start of treatment. The concentration of histamine required to increase total airway obstruction by 35% (PC35) was significantly reduced during treatment with clenbuterol (mean change, 11.5 mg/mL), compared with during administration of the placebo (mean change, -1.56 mg/mL), with a peak effect at 14 days. Tachyphylaxis was evident by day 21, with 7 of 8 horses having a PC35 below the baseline value (mean change, -0.48 mg/mL), which returned to baseline values during the washout period. No effect of clenbuterol was seen in sweat response to epinephrine administration. Clenbuterol initially reduced airway sensitivity to inhaled histamine, but tachyphylaxis that resulted in increased airway reactivity was evident by day 21. Although no effects on sweating were detected, the technique may not have been sensitive enough to identify subtle changes. Prolonged administration of clenbuterol likely results in a clinically important reduction in its bronchodilatory effects.

Radiographic scoring lacks predictive value in inflammatory airway disease

Diagnosis of inflammatory airway disease (IAD) currently rests upon the results of bronchoalveolar lavage (BAL) cytology, lung function testing and histamine bronchoprovocation (HBP), none of which provides direct information about structural change in the lung. That thoracic radiography might better portray structural change in the lungs and therefore offer a good clinical assessment of IAD. A radiographic scoring system was developed to assess the extent of bronchial and interstitial pattern on thoracic radiographs in the dorsocaudal, dorsocranial and caudoventral regions in 16 control horses and 33 horses with IAD. Mean scores were compared to ascertain whether thoracic radiographs could distinguish between the 2 groups. In order to determine whether independent observers reliably scored radiographs similarly, an inter-rater reliability score was employed for each radiographic observation. Correlations between radiographic scores, BAL cytology, lung function testing using the forced oscillatory technique and HBP were examined. Inter-rater reliability was only moderate. Radiographic scoring demonstrated no differences between the 2 groups. There were no correlations among BAL cytology, lung function testing, HBP and radiographic scores. Thoracic radiographs are a low-yield diagnostic modality in horses with a clinical history compatible with IAD. In the absence of clinical evidence of more extensive, infectious disease, thoracic radiographs neither refine nor improve diagnosis of IAD, but increase diagnostic costs.

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.

Histamine bronchoprovocation does not affect bronchoalveolar lavage fluid cytology, gene expression and protein concentrations of IL-4, IL-8 and IFN-γ

In diagnosing inflammatory airway disease (IAD) in performance horses, a histamine bronchoprovocation (HBP) test is often performed. In previously published studies, HBP is usually undertaken prior to cytological examination of the bronchoalveolar lavage (BAL) cells. The purpose of this study was to determine if HBP alters (1) the total nucleated cell numbers and distribution in BAL fluid (BALF) and (2) the mRNA and protein concentrations of selected cytokines in BAL cells and BALF, respectively. BALF was initially collected endoscopically from the right middle or diaphragmatic lung lobe in eight healthy young Standardbred horses. Five to six days later, HBP was performed by aerosolization of histamine (8 mg) over a 2 min period. BALF was again collected within 2–4 h of the HBP from the left middle or diaphragmatic lung lobe. In both samples, total and differential WBC counts were obtained. The gene expressions of interleukin-4 (IL-4), IL-8, interferon-γ (IFN-γ) and β-actin in BAL cells were measured using real-time RT-PCR. The cytokine protein concentrations were measured in the BALF using ELISA. HBP was not associated with either a change in the total BAL cell number or in the distribution of the BAL cells. BAL cell expression of IL-4, IL-8 and IFN-γ, detected in all samples with the exception of IL-4 in one horse (post-HBP), was not altered as a result of HBP. HBP was not associated with a significant change in IL-8 or IFN-γ concentrations in the BALF. IL-4 protein was undetectable in BALF either prior to or following HBP. We conclude that HBP can precede BALF collection performed within 2–4 h of the former without affecting selected parameters analysed in the BAL cells or BALF.

Characterisation of the acute and reversible airway inflammation induced by cadmium chloride inhalation in healthy dogs and evaluation of the effects of salbutamol and prednisolone

The aims of this study were firstly to characterise a model of subclinical and reversible bronchial inflammation induced by cadmium chloride inhalation in healthy dogs and then to examine the effect of prednisolone or salbutamol treatment on the resulting bronchitis. The model characterisation and the effects of treatment were studied using clinical symptoms, haematology, thoracic radiography, bronchoscopy and bronchoalveolar lavage, barometric whole-body plethysmography and histamine broncho-provocation tests. In addition, the activity of matrix metalloproteinases (MMP)-2 and -9 were determined in serum and bronchoalveolar lavage fluid (BALF). Cadmium inhalation induced: (1) a transient bronchial inflammation, dominated by neutrophils; (2) a neutrophilia of the blood that persisted for up to 4 weeks; (3) a transient increased bronchial reactivity, and (4) a significant increase in MMP-9 activity in the BALF. Prednisolone treatment reduced the influx of inflammatory cells into the BALF, but not significantly, had no effect on pulmonary function, and did not reduce of airway hypersensitivity. Salbutamol had almost no effect on any of the parameters investigated.

Serum concentration of C-reactive protein is not a good marker of bronchial hyperresponsiveness

Introduction:Asthmatic inflammation is responsible for vital features of the disease, including bronchial hyperresponsiveness (BHR). At present we do not have precise markers for monitoring asthmatic inflammation. C-reactive protein (CRP), a marker of systemic inflammation, seemed to be a factor which could also reflect the level of asthmatic inflammation expressed by BHR. Therefore the relationship between CRP concentration and BHR was evaluated.Materials and Methods:One hundred and two patients entered the study. A skin prick test with a broad spectrum of common aeroallergens as well as baseline spirometry and a histamine bronchoprovocation test were performed in each subject. Blood samples for high-sensitivity CRP (hsCRP) measurement were taken before the bronchial challenge tests.Results:Serum hsCRP concentrations ranged from 0.20 to 14.5 mg/l (median: 1.2 mg/l, 25–75% quartiles: 0.6–2.4). Positive skin prick tests were found in 26 subjects. Bronchial hyperresponsiveness was confirmed in 42 patients (first subgroup), while 60 subjects did not demonstrate BHR (second subgroup). Among the patients with BHR, asthma was diagnosed in 33 cases and Corrao syndrome in 9. In both subgroups, serum hsCRP concentrations had similar levels (median: 1.4 mg/l, 25–75% quartiles: 0.8–2.4 and median: 0.9 mg/l, 25–75% quartiles: 0.5–2.8, respectively; p=0.297). There was no statistically significant correlation (r= −0.163, p=0.302) between serum hsCRP concentration and the level of BHR expressed as the 20% provocative concentration for histamine. In addition, hsCRP serum concentration, after adjustment for age, atopy, body mass index, and gender, was not a significant predictor of positive histamine bronchoprovocation test results (p=0.22, OR=0.86, 95% CI).Conclusions:Serum hsCRP concentration is not a good marker of BHR, which is mainly dependent on asthmatic inflammation and is measured during bronchial challenge with histamine. This finding is important for interpreting and discussing results obtained from epidemiological and population-based studies on relationships between either CRP concentration and BHR or local and systemic inflammation.

The Use of Oscillometry as a Measure of Airway Responsiveness in Asthmatic Children After Histamine and Methacholine Bronchoprovocation with Dosimeter-MedicAid and DeVilbiss Nebulizers

To explore the use of oscillometry as a measure of airway responsiveness, 69 asthmatic children underwent histamine and methacholine bronchoprovocation using dosimeter-MedicAid (Jaeger Co.; Germany) and DeVilbiss nebulizers (DeVilbiss, Bornemouth; England). The mean increase in R5 resistance in challenge testing measured after methacholine with the dosimeter-MedicAid nebulizer was 77.14% compared with 65.05% using histamine. Using the dosimeter-DeVilbiss nebulizer, the mean increases in R5 resistance following methacholine and histamine testing were 57.50% and 59.36%, respectively. The resistance R5 over R20 significantly correlated with forced expiratory volume in 1 second (FEV1). The MedicAid produced a more aggressive challenge than the DeVilbliss nebulizer. Oscillometry can be used to monitor the level of airway hyperresponsiveness following bronchoprovocation tests.

Exhaled nitric oxide levels in military recruits with new onset asthma

Approximately 800 United States Air Force basic military trainees (BMTs) are diagnosed with asthma, annually, resulting in separation from the military. With training costs of approximately 10,000 dollars/person, around 8 million dollarsis lost per year. Improved methods in diagnosing asthma would be beneficial. The aim of this study was to determine the fraction of exhaled nitric oxide (FENO), a marker of airway inflammation, in a military recruit population referred for an asthma evaluation. In BMTs referred for respiratory complaints during basic training, FENO levels were determined before an asthma evaluation consisting of a history, physical, baseline spirometry, and histamine bronchoprovocation. Of 172 BMTs who had symptoms suggestive of asthma and underwent histamine bronchoprovocation, 80% were diagnosed with asthma. FENO levels were significantly higher in asthmatic patients than nonasthmatic patients (mean, 30 parts per billion [ppb] versus 19 ppb, p < 0.001; median, 21 ppb versus 17 ppb, p < 0.02). Various FENO cutoff points provided a range of sensitivity and specificity for the diagnosis of asthma. However, an optimal FENO cutoff level for asthma was not obtained. An FENO value of 10.5 ppb provided a sensitivity of 86% for the diagnosis of asthma, but specificity was only 21%. In contrast, an FENO value of 46 ppb provided 100% specificity but only 17% sensitivity. FENO levels were significantly elevated in BMTs diagnosed with asthma but the lack of an optimal cutoff level limits the test as a diagnostic tool for asthma. Additional studies are necessary to determine the value of FENO for asthma screening in a military population.

Respiratory atopic disease, Ascaris‐immunoglobulin E and tuberculin testing in urban South African children

Epidemiological relation of intestinal helminth infection and atopic disease, both associated with a T-helper (Th) 2 immune response, is controversial, as it has been reported that helminth infection may either suppress or pre-dispose to atopic disease. This relation has not been tested in an area with a high burden of Mycobacterium tuberculosis (MTB) infection, a known Th1-stimulating infection. To study the association of intestinal helminth infection and atopic disease in a community where helminth infection is endemic and MTB infection is high. Three-hundred and fifty-nine randomly selected children aged 6-14 years from a poor urban suburb were tested with allergy questionnaire, skin prick test (SPT) to common aeroallergens, Ascaris-specific IgE (Ascaris-sIgE), fecal examination for pathogenic intestinal helminths and tuberculin skin testing (TST). Histamine bronchoprovocation was tested in the group of children aged 10 years and older. were corrected for demographic variables, socioeconomic status, parental allergy, environmental tobacco smoke (ETS) exposure in the household, recent anthelminthic treatment and for clustering in the sampling unit. Results Ascaris-sIgE was elevated in 48% of children, Ascaris eggs were found in 15% and TST was positive in 53%. Children with elevated Ascaris-sIgE had significantly increased risk of positive SPT to aeroallergens, particularly house dust mite, atopic asthma (ever and recent), atopic rhinitis (ever and recent) and increased atopy-related bronchial hyper-responsiveness. In children with negative TST (<10 mm), elevated Ascaris-sIgE was associated with significantly increased risk of atopic symptoms (adjusted odds ratio (OR(adj)) 6.5; 95% confidence interval (CI) 1.9-22.4), whereas in those with positive TST (>/=10 mm) this association disappeared (OR(adj) 0.96; 95% CI 0.4-2.8). These results suggest that immune response to Ascaris (Ascaris-sIgE) may be a risk factor of atopic disease in populations exposed to mild Ascaris infection and that MTB infection may be protective against this risk, probably by stimulation of anti-inflammatory networks.

Dalhousie dyspnea scales: Pictorial scales to measure dyspnea during induced bronchoconstriction

The aim of this study was to validate our Dalhousie Dyspnea Scales in children referred for histamine bronchoprovocation challenge. Seventy-four children rated their dyspnea after each FEV(1) measurement following inhalation of doubling histamine concentrations from 0.125 to 8.0 mg/ml by the standard tidal breathing method. Serial FEV(1) and dyspnea rating using the Dalhousie Dyspnea Scales were recorded and Kendall's tau was computed for dyspnea rating versus fall in FEV(1). Subjects were split into those with positive (DeltaFEV(1) >or= 20% with PC(20) <or= 8 mg/ml) or negative histamine challenge test. During histamine inhalation, dyspnea ratings on each of the subscales rose as FEV(1) fell across subjects, whether or not they were histamine-responsive (main effect), and then fell dramatically following relief of induced obstruction by bronchodilator.The Dalhousie Dyspnea Scales are useful and accurate tools to measure dyspnea due to bronchoconstriction in children.

Airway inflammation and cough sensitivity in cough‐variant asthma

Mechanisms underlying cough and bronchoconstriction in patients with cough-variant asthma (CVA) are not well established. Differences in location or degree of activation of eosinophils and allergic cytokines have been suggested as the likely causes. To address this issue, we have carried out a comparative study of airway inflammatory markers between patients with CVA and classic asthma (CA). The relationship between these markers with airway hyperresponsiveness (AHR) and cough sensitivity has also been studied. Twenty-seven non-smokers and steroid-naive patients with CVA (12) and CA (15) were examined. Capsaicin challenge, histamine bronchoprovocation test, nitric oxide levels in exhaled air and sputum induction were performed in all of them. Differential cell sputum recount and supernatant concentrations of eosinophil granule-derived cationic proteins (ECP), interleukin (IL)5, IL8 and tumour necrosis factor (TNF)-alpha were also measured. There were no significant differences in either the inflammatory pattern of soluble markers or differential cell counts between CA and CVA. Histamine PC20 was correlated with IL-5 in CVA, whereas it was associated with sputum eosinophilia in CA. Cough sensitivity (log C5) and histamine PC20 were inversely related in CA. Although the pattern of inflammatory sputum markers in patients with asthma and cough-variant asthma is similar, its relation with bronchial hyperreactivity and cough sensitivity is different in each group.

Cough reflex in allergic dogs

This study investigated the effects of antigen challenge on the cough reflex in dogs that were neonatally sensitized to ragweed. Tidal volume (VT), respiratory rate (f), pulmonary resistance (RL), dynamic lung compliance (CDyn) and the number and amplitude (increase in mean peak expiratory pressure) of coughs induced by mechanical stimulation of the intrathoracic trachea were measured in propofol-anesthetized dogs. Aerosolized ragweed challenge had no effect to induce spontaneous cough but increased f and RL and reduced VT and CDyn. Mechanical stimulation of the intrathoracic trachea at this time produced 19±5 coughs with an average increase in cough amplitude of 11±1 cm H2O which differed significantly from the number (9±2 coughs) and amplitude (30±5.5 cm H2O) of mechanically induced coughs after treatment with aerosolized saline. Both the number and amplitude of mechanically induced coughs returned to baseline values by 24–48 h after the ragweed challenge. Similar results were obtained after challenge with aerosolized histamine (0.3–1% histamine) that did not induce spontaneous coughs but increased f, reduced VT and decreased CDyn and increased the number but reduced the amplitude of the mechanically induced coughs. In conclusion, both antigen and histamine bronchoprovocation changed the characteristics of the mechanically induced cough in dogs to a response of increased cough number but reduced mean expiratory cough amplitude.