Relationship between exhaled carbon monoxide and airway hyperresponsiveness in asthmatic patients.

The study objectives were to analyze the changes in exhaled carbon monoxide (COex) induced by histamine provocation challenge in asthmatic patients and to evaluate the relationship between COex and airway sensitivity and reactivity. Levels of COex were measured in 105 nonsmoking mildly asthmatic subjects before and after histamine provocation challenge. Dose-response curves were characterized by their sensitivity (PD20) and reactivity. Dose-response slope (DRS), continuous index of responsiveness (CIR), and bronchial reactivity index (BRI) were determined as reactivity indices. Bronchial challenge was positive for 47 subjects and negative for 58. The COex levels rose significantly after bronchial challenge in the positive response group (4.49 +/- 0.4 vs. 5.74 +/- 0.57 ppm, p = 0.025) and in the negative response group (2.84 +/- 0.25 vs. 4.00 +/- 0.41 ppm, p = 0.000). An inverse relation between basal COex and PD20 was found (r = -0.318, p = 0.030). In all subjects, a proportional direct relationship between COex and DRS (r = 0.214, p = 0.015), CIR (r = 0.401, p = 0.000), and BRI (r = 0.208, p = 0.012) was observed. On stepwise multiple linear regression analysis, COex only significantly correlated with CIR (multiple r2 = 0.174, p = 0.000). In conclusion, exhaled CO determination is a noninvasive inflammatory marker of the respiratory tract, which shows an acceptable association with airway hyperresponsiveness.     

Relationship Between Exhaled Carbon Monoxide and Airway Hyperresponsiveness in Asthmatic Patients

The study objectives were to analyze the changes in exhaled carbon monoxide (COex) induced by histamine provocation challenge in asthmatic patients and to evaluate the relationship between COex and airway sensitivity and reactivity. Levels of COex were measured in 105 nonsmoking mildly asthmatic subjects before and after histamine provocation challenge. Dose‐response curves were characterized by their sensitivity (PD₂₀) and reactivity. Dose‐response slope (DRS), continuous index of responsiveness (CIR), and bronchial reactivity index (BRI) were determined as reactivity indices. Bronchial challenge was positive for 47 subjects and negative for 58. The COex levels rose significantly after bronchial challenge in the positive response group (4.49 ± 0.4 vs. 5.74 ± 0.57 ppm, p = 0.025) and in the negative response group (2.84 ± 0.25 vs 4.00 ± 0.41 ppm, p = 0.000). An inverse relation between basal COex and PD₂₀ was found (r = ? 0.318, p = 0.030). In all subjects, a proportional direct relationship between COex and DRS (r = 0.214, p = 0.015), CIR (r = 0.401, p = 0.000), and BRI (r = 0.208, p = 0.012) was observed. On stepwise multiple linear regression analysis, COex only significantly correlated with CIR (multiple r² = 0.174, p = 0.000). In conclusion, exhaled CO determination is a noninvasive inflammatory marker of the respiratory tract, which shows an acceptable association with airway hyperresponsiveness.     

Usefulness of bronchial reactivity analysis in the diagnosis of bronchial asthma in patients with bronchial hyperresponsiveness

We examined the usefulness of some bronchial reactivity indices to identify bronchial asthma in patients with airway hyperresponsiveness. Eighty-eight consecutive patients with positive response to histamine bronchial challenge (> or = 20% fall in FEV1) were included in the study. Dose-response curves were characterised by their sensitivity (PD20) and reactivity. Dose-response slope, continuous index of responsiveness (CIR) and bronchial reactivity index (BRI) with respect to baseline and post-diluent baseline values were determined as reactivity indices. The clinical diagnosis remaining in the case history 2 years after the bronchial challenge was considered the definitive diagnosis. Asthmatic patients had higher baseline BRI (12.121+/-0.412 vs. 11.615+/-0.201; P<0.001) and post-diluent baseline BRI (12.054+/-0.368 vs. 11.563+/-0.531; P = 0.003) than other subjects. Area beneath their receiver operating characteristic (ROC) curve was 82.68% (standard error: 0.77) for the baseline BRI and 81.73 (standard error: 0.76). By multiple logistic regression analysis, baseline BRI was the only independent variable identified as a predictor for diagnosis of bronchial asthma (r = 0.387, P = 0.0007). A cut-off of 11.76 for baseline BRI reached an 87.2% sensitivity and an 80% specificity for bronchial asthma diagnosis. In conclusion, BRI calculated with respect to baseline FEV1 should be useful in identifying asthmatic patients among subjects with airway hyperresponsiveness.     

Atopic and Nonatopic Asthma in Children

In 155 asthmatic children we have studied the relationship between prick test positivity and a set of genetic factors previously found to be associated with bronchial asthma. Among these factors, MN system (p = 0.009) and age at onset of symptoms (p = 0.05) are the most important variables separating prick test negative from prick test positive children. MN and age at onset influence independently prick test positivity pointing to an additive effect of the two variables. M phenotype appears correlated positively with an increased susceptibility to nonallergic asthma in all age groups, whereas N phenotype appears correlated positively with age at onset but in allergic asthma only. The MN system codifies for glycophorin A, a sialoglycoprotein that represents a major ligand for several bacteria and viruses that recognize the N-acetylneuraminic acid present in this protein. The present data suggest that genetic variability in this system might influence bacterial and viral competition and mucosal damage influencing susceptibility to asthmatic reactions in absence of IgE hyperproduction.     

Peripheral Inflammation in Patients with Asthmatic Symptoms but Normal Lung Function

Some patients with asthmatic symptoms and eosinophilic airway inflammation have normal lung function and thus do not meet the current diagnostic criteria of asthma. Exhaled nitric oxide (NO) measurement at multiple exhalation flow rates can be used to assess alveolar and bronchial NO output and inflammation. We tested whether alveolar or bronchial NO output is increased in subjects having asthmatic symptoms but normal lung function. Exhaled NO concentration was measured at three exhalation flow rates (100, 175, and 370 mL/s) to assess alveolar NO concentration and bronchial NO flux in 23 patients with asthmatic symptoms but normal lung function (“asthmatic symptoms group”), 40 patients with asthma, and 40 healthy control subjects. The asthmatic symptoms group had increased bronchial NO flux (1.7 ± 0.3 nL/s, p = 0.016) and alveolar NO concentration (1.8 ± 0.2 parts per billiant (ppb), p = 0.010) compared with healthy controls (0.7 ± 0.1 nL/s and 1.0 ± 0.1 ppb, respectively). Patients with asthma had even higher bronchial NO flux (2.5 ± 0.3 nL/s, p = 0.024) but normal alveolar NO concentration (1.1 ± 0.2 ppb, p = 0.664). In asthmatic symptoms group, alveolar NO concentration correlated positively with blood eosinophil count and negatively with small airway function (FEF_50% and FEF_75%). In conclusion, patients with asthmatic symptoms but normal lung function have increased alveolar NO concentration and mildly elevated bronchial NO flux suggesting a more peripheral inflammation than in patients with asthma.     

Cellular events in the bronchi in mild asthma and after bronchial provocation

We have undertaken detailed cellular and ultrastructural examination of bronchial biopsies and bronchial lavage fluid from allergic asthmatic patients in order to determine the nature and degree of the inflammatory processes in mild allergic asthma. Eight atopic asthmatic patients (mean PC20 histamine, 0.90 mg/ml) and four nonasthmatic control subjects underwent fiberoptic bronchoscopy. All asthmatic subjects were clinically stable for 2 wk prior to bronchoscopy and required either no treatment or inhaled albuterol alone. A single 50-ml bronchial wash was undertaken, followed by endobronchial biopsy of subcarinae. These procedures were repeated in the asthmatic subjects 18 h after bronchial provocation with allergen or methacholine. Subsequently, all subjects underwent bronchial reactivity testing with inhaled histamine. The clinical and physiologic data were not revealed to the pathologist interpreting the specimens. The asthmatic subjects shed a significantly greater number of epithelial cells into the lavage fluid than did the nonasthmatic subjects (7.23 versus 1.48 x 10(4)/ml, p = 0.048). There was a statistically significant inverse correlation between the lavage epithelial cell count and bronchial reactivity (rho = -0.64, p = 0.03). In the asthmatic subjects, but not in the control subjects, there was extensive deposition of collagen beneath the epithelial basement membrane, mast cell degranulation, and mucosal infiltration by eosinophils, which exhibited morphologic evidence of activation. Eosinophils, monocytes, and platelets were found in contact with the vascular endothelium, with emigration of eosinophils and monocytes in the asthmatic subjects. These changes were found irrespective of bronchial challenge with allergen. We conclude that allergic asthma is accompanied by extensive inflammatory changes in the airways, even in mild clinical and subclinical disease.     

A Bronchial Response Comparison of Exercise and Methacholine in Asthmatic Subjects

The authors compared the inhaled methacholine and exercise responses in 22 stable unmedicated asthmatic patients. The exercise and methacholine challenges were performed at one to three week intervals. Bronchial responsiveness to methacholine was measured in relation to the concentration of methacholine (PC₂₀M). The response to exercise was expressed as the percentage of fall in FEV₁, from the pre-exercise FEV₁ The findings showed that 21 of 22 subjects demonstrated a fall in FEV₁, of more than 20% after methacholine challenge, while only 9/22 subjects experienced a similar decrease in FEV₁. All 9 of these positive response exercise cases completed three consecutive exercise challenges prior to the methacholine challenge. Of these cases, five were refractory to the repeated exercise challenge, and the PD₂₀M at the nonexercise stage was significantly lower than the postexercise state. In fact, the methacholine challenge sensitivity actually decreased (PD₂₀ increased) after repeated exercise. The authors concluded that methacholine seems to be a more sensitive bronchial provocation test than exercise. Second, only 55.6% of the exercise test-positive subjects were refractory to the second exercise challenge. Therefore, other factors besides the release of mediators should be considered in exercise induced asthma. Third, methacholine sensitivity actually decreased (PD₂₀ increases) after repeat exercise challenge.     

Esophageal acid perfusion, airway function, and symptoms in asthmatic patients with marked bronchial hyperreactivity

It is believed that GER can trigger asthma by the stimulation of acid-sensitive receptors in the esophagus. The aim of this study was to determine whether esophageal acid stimulation in asthmatic patients can provoke clinically detectable bronchospasm and if a possible response is correlated to bronchial reactivity. Eight patients with chronic asthma and GER disease were investigated on three occasions with a histamine challenge test followed by acid provocation of the esophagus. Assessment of bronchial function was made by FEV1, chest auscultation, and respiratory symptoms. While symptoms and signs of bronchoconstriction induced by esophageal acid stimulation were not detected clinically on any occasion, there was a significant correlation between histamine reactivity and the subclinical bronchospasm following acid provocation. It is concluded that esophageal acid stimulation during daytime in the majority of asthmatic patients is not a strong and immediate trigger of asthma.     

Effect of hyposensitization upon the immediate and late asthmatic reaction and upon histamine reactivity in patients allergic to house dust mite (Dermatophagoides pteronyssinus).

The effect of hyposensitization (HS) upon the allergen evoked immediate asthmatic reaction (IAR), late asthmatic reaction (LAR) and upon bronchial reactivity towards histamine was examined. Eighteen young asthmatic patients were studied using a double-blind, placebo-controlled design. All were allergic to house dust mite (HDM) and demonstrated an IAR and a LAR after bronchial provocation with HDM. Furthermore, all, except one child, demonstrated bronchial hyperreactivity towards histamine (median provocative dose producing a 20% fall in forced expiratory volume in one second (PD20) histamine = 0.19 mg.ml-1, range: 0.02-8 mg.ml-1). The subjects were randomly divided into two groups to receive HDM or placebo injections during one year. After the one year period, the IAR was less severe in the subjects who received HDM injections (p = 0.02), while this reduction was not observed in the subjects who received placebo injections. Also, in the HDM group a small but significant increase of the median PD20 HDM was observed (p = 0.04). Furthermore, the LAR was less severe in the subjects who received HDM injections (p = 0.02), while the subjects who received placebo injections showed the same severity of LAR after one year (p = 0.44). Histamine reactivity did not change after HDM injections or after placebo injections. Thus, HS reduces the severity of the IAR and LAR without any change in histamine reactivity.     

Dietary Intake of Soy Genistein is Associated with Lung Function in Patients with Asthma

To determine if micronutrient intake is associated with asthma severity, we administered the Block food frequency questionnaire to participants in a randomized clinical trial of the safety of influenza vaccine for asthmatics. The nutrition substudy included 1033 participants, aged 12-75. Intake of antioxidant vitamins, soy isoflavones, total fruits and vegetables, fats, and fiber was compared with asthma severity at baseline [forced expiratory volume in 1 second (FEV₁), peak expiratory flow rate (PEF), asthma symptoms] and the rate of asthma exacerbations during the 2 weeks following influenza vaccination. The only nutrient that had a consistent association with asthma severity was genistein, a soy isoflavone. None of the nutrients evaluated were related to asthma exacerbation rate when adjusted for known confounders. The FEV₁ in genistein consumers of at least 250 µg/1000 Kcal/day was 82.1% predicted, 79.9% predicted for those who consumed between 1 and 249 µg/1000 kcal, and 76.2% predicted in genistein nonconsumers (p = 0.006); the PEF was 82.7% predicted, 80.8% predicted, and 78.3% predicted, respectively (p = 0.009). There were no differences in the Asthma Symptom Utility Index (ASUI). We could not account for these results based on differences in demographics, body mass index, or consumption of other nutrients. Thus, increasing consumption of genistein is associated with better lung function in patients with asthma. Further studies are needed to determine whether dietary supplementation with genistein can reduce asthma severity.     

Bronchial reactivity increases soon after the immediate response in dual-responding asthmatic subjects

To determine whether bronchial reactivity is augmented soon after an allergen-induced immediate asthmatic response, we compared reactivity to histamine before and immediately upon resolution of the immediate asthmatic response in seven subjects with mild asthma who were known to develop dual asthmatic responses after inhalation of Kentucky bluegrass allergen. Using a body plethysmograph and quiet breathing technique, specific airway resistance (SRaw) and reactivity to aerosol histamine were assessed on two days prior to allergenic challenge. The dose of histamine that doubled SRaw (PC200His) was determined by interpolation from histamine dose-response curves. On the day of allergenic challenge, each subject inhaled a concentration that was sufficient to induce a dual asthmatic response. Upon resolution of the immediate asthmatic response (45 to 105 minutes) after allergen, the PC200His in all cases had decreased more than 50 percent of its original value (PC200His for the group was 0.29 +/- 1.42 mg/ml [mean +/- SE], compared to 0.84 +/- 1.23 mg/ml initially). Seven or more days after the allergen, each subject had a PC200His comparable to original values. Our data indicate that airway reactivity in dual-responding asthmatic subjects markedly increases soon after the immediate asthmatic response and much before the late asthmatic response manifests clinically. Whether this early increase in bronchial reactivity is a putative requirement for, or shares common characteristics with the late asthmatic response requires further study.     

Adenosine 5'-monophosphate increases levels of leukotrienes in breath condensate in asthma

Hyperresponsiveness (AHR) is a key physiological abnormality in asthma. In clinical and research studies AHR is measured bronchial challenge, with methacholine (MCh), but more recently with adenosine-5'-monophosphate (AMP). In the search for markers of airway inflammation in asthmatic patients, we measured the concentrations of histamine and cysteinyl-leukotrienes (cys-LTs) before and after MCh and AMP challenges in the exhaled breath condensate of 13 patients with mild asthma (FEV1 78.5%pred) and nine healthy non-smokers, using specific enzyme immunoassays. With methacholine challenge we did not find any differences between asthmatics and normal subjects in the pre- and post-challenge concentrations of cys-LTs: 27.2+/-1.4 vs. 29.2+/-1.2 pg/ml and 26.3+/-2.2 vs. 27.5+/-4.2 pg/ml, respectively or histamine: 5.1+/-0.4 vs. 5.1+/-0.6 nM and 4.5+/-0.4 vs. 4.4+/-0.3 nM; P>0.05). In asthmatic patients cys-LT levels were significantly higher after AMP challenge (56.2+/-9.7 vs. 31.7+/-6.9 pg/ml; P<0.05); but there was no difference in healthy subjects (27.2+/-4.6 vs. 30.3+/-4.7 pg/ml). There was no difference in histamine concentrations in asthmatic (5.9+/-1.8 vs. 4.5+/-0.5 nM), or healthy subjects (5.5+/-0.4 vs.5.7+/-0.9 nM) after AMP challenge. In conclusion, our results show that the cys-LTs are increased in exhaled breath condensate after AMP challenge, which may indicate that the AMP acts indirectly by releasing cys-LTs from primed mast cells. The detection of LTs and histamine in exhaled breath condensate may be useful in monitoring asthma.     

Cut-off points defining normal and asthmatic bronchial reactivity to exercise and inhalation challenges in children and young adults.

An analysis was undertaken to determine the optimal cut-off separating an asthmatic from a normal response to a bronchial provocation challenge by exercise and the inhalation of methacholine or histamine in children and young adults. Data were extracted, after appropriate correction, from published studies available in Medline of large random populations that complied with preset criteria of suitability for analysis, and the distribution of bronchial reactivity in the healthy population for exercise and inhalation challenges were derived. Studies on the response to exercise and methacholine inhalation in 232 young asthmatics of varying severity were carried out by the authors and the distribution of bronchial reactivity of a young asthmatic population obtained. Comparisons of the sensitivity and specificity of the challenges were aided by the construction of receiver operating characteristic curves. The optimal cut-off point of the fall in forced expiratory volume in one second (FEV1) after exercise was 13%, with a sensitivity (power) of 63% and specificity of 94%. For inhalation challenges, the optimal cut-off point for the dose of methacholine or histamine causing a 20% fall in FEV1 was 6.6 micromol, with a sensitivity of 92% and a specificity of 89%. The cut-off values were not materially affected by the severity of the asthma and provide objective data with which to evaluate the results of bronchial provocation challenges in children and young adults.     

Prednisolone Hastens Recovery from Histamine-Induced Bronchospasm in Asthmatics

Short-term treatment with oral steroids is very effective in controlling symptoms and improving lung function in asthma but has not been shown unequivocally to reduce bronchial hyperresponsiveness. Recently it has been shown to increase the activities of sodium-potassium and calcium adenosine triphosphatases, enzymes that regulate intracellular calcium levels. This action may be expected to promote recovery of cells from an excitatory stimulus. The present study was carried out to determine how prednisolone modulates airway response to histamine, including recovery from induced bronchospasm in asthmatics. Spirometry and measurement of bronchial responsiveness (forced expiratory volume in 1 sec [FEV₁] and concentration of histamine causing a 20% reduction FEV₁ [PD₂₀ FEV₁]) to inhaled histamine were carried out in 10 clinically stable asthmatics. Subsequently, all of the patients were prescribed oral prednisolone, 0.6-0.75 mg/kg body weight for 1 week. At the end of 1 week, spirometry was repeated and bronchial reactivity was measured again. Comparison of PD₂₀ FEV, values before and after treatment (geometric means 0.66 and 0.81 mg/mL, respectively) for the whole group did not show any significant change. The mean ± SD time for 95% recovery from histamine-induced bronchospasm was 33.00 ± 19.47 min before treatment and decreased significantly to 18.00 ± 7.88 min after treatment. It was concluded that short-term benefits from oral prednisolone do not result from changes in bronchial responsiveness. These benefits may be related to effects on mechanisms that lead to recovery from an excitatory stimulus.     

Cold air as a bronchial provocation technique. Reproducibility and comparison with histamine and methacholine inhalation

Bronchial provocation testing with cold air was carried out on 36 asthmatic and 13 normal subjects in order to assess the reproducibility and clinical relevance of the technique as a test of airways reactivity. Sixteen subjects underwent repeat testing after an interval of two to three weeks. Using a least squares linear regression analysis, the technique was highly reproducible, with a correlation of r = 0.93 (p less than 0.001). The 21 asthmatic subjects who had exercise-provoked symptoms required a significantly lower level of ventilation of cold air to produce a 35 percent drop in specific airways conductance (PD35) than did those who had no exercise-induced asthma (33.9 L min-1 vs 45.8 L min-1; p less than 0.02). Subjects requiring no regular treatment for their asthma had a geometric mean PD35 of 62.6 L min-1, significantly higher than those requiring inhaled therapy (44.9 L min-1; p less than 0.005). Subjects requiring oral in addition to inhaled treatment had the lowest PD35 (23.6 L min-1; p less than 0.02). Atopic status did not appear to influence the response. There was a strong correlation between the PD35 to cold air and to histamine (r = 0.92; p less than 0.001) and between the PD35 to cold air and to methacholine (r = 0.86; p less than 0.001). The three techniques of assessing bronchial reactivity were equally successful in separating the normal and asthmatic groups. The results indicate that cold air provocation may be reliably and reproducibly used to assess bronchial reactivity. The use of a naturally-occurring stimulus of asthma in all subjects has great potential as an investigational technique.     

The Relationship of Exhaled Nitric Oxide to Airway Inflammation and Responsiveness in Children

Exhaled nitric oxide (eNO) is a potential tool in epidemiological studies of asthma. It was hypothesized that in a cross-sectional survey of asthma in adolescent children, eNO may contribute to the detection of this disease. A cohort of Australian school children in two educational years (n = 107, aged 14.7 ± 2.3 years, 42.9% female) were surveyed in terms of exhaled nitric oxide (eNO), which was compared with other indicators of asthma: asthma symptoms, atopy [skin prick tests (SPT)], hypertonic saline bronchial reactivity, sputum inflammatory cells and eosinophilic cationic protein. Significant positive correlations were found with eNO and number of positive skin prick tests (p = 0.001; n = 98), symptoms (p = 0.05; n = 107), sputum eosinophils (p = 0.025; n = 83), and sputum eosinophilic cationic protein (p = 0.009; n = 83). There was no significant relationship with airway hyperresponsiveness (p = 0.3; n = 15). eNO had a negative predictive value for asthma of 83%, and a positive predictive value of 54%, which is comparable with most current tests for diagnosing asthma. eNO appears to be a useful indicator of atopy and airway inflammation, but in this population it was not closely related to airway hyperresponsiveness.     

Perception of respiratory sensation assessed by means of histamine challenge and threshold loading tests

BACKGROUND: Some asthmatic patients perceive the severity of their disease rather poorly. These patients may not receive optimal therapy because of underpresentation of their respiratory symptoms. It is therefore important to identify these patients. The present study evaluates a new threshold loading device for measuring the perception of respiratory sensation. This method for measuring the perception of respiratory sensation may be a viable alternative to the bronchial provocation test. The aim of the present study was to investigate whether the assessment of the perception of respiratory sensation based on a threshold loading test (inspiratory and expiratory) identifies the same subjects as poor perceivers as compared to assessment by histamine bronchial provocation test. METHOD: In 36 subjects, the perception of respiratory sensation through a threshold loading device was compared to the perception of respiratory sensation during a histamine provocation test. Each test was performed with scoring of the magnitude of the respiratory sensation on a visual analog scale (VAS). The magnitude of the stimulus intensity was indicated by the percentage of decrease in FEV(1) during the histamine challenge test and by the percentage of the subject's maximum mouth pressure (percent maximal inspiratory pressure and percent maximal expiratory pressure) during the threshold loading test. The relationship between VAS values and the stimulus intensity was analyzed by determining the linear regression coefficient between the two parameters. RESULTS: No relationship was found between the perception of the sensation induced by the histamine challenge and that during breathing through a threshold loading device for both inspiration (Rs = 0.15; p = 0.40) and expiration (Rs = 0.13; p = 0.47). We did find a significant relation between the perception of respiratory sensation during the inspiratory and expiratory threshold loading test (Rs = 0.67; p = 0. 0001). Furthermore, we defined a subgroup of patients of special interest: those with low symptoms of breathlessness and high bronchial responsiveness. Compared to the inspiratory and expiratory threshold loading test, the histamine challenge test identified more patients in the special interest group as poorest perceivers. CONCLUSION: The measurement of perception by means of a threshold loading device and a histamine provocation test did not identify the same subjects as poor perceivers, probably because we did not measure the patient's perceptiveness for exactly the same stimuli. In the population with relatively more severe asthma and very low symptoms of breathlessness, the histamine-induced bronchoconstriction test identified more patients as poorest perceivers compared to the threshold loading test.     

Exhaled Nitric Oxide Predicts Asthma Exacerbation

The fraction of exhaled nitric oxide (FeNO) is elevated in asthmatics compared to normal subjects. Many studies have demonstrated that FeNO correlates with other markers of airway inflammation. The purpose of this study was to assess the clinical utility of routine monitoring of FeNO in determining its ability to predict future asthma exacerbations compared with other standard clinical measures of spirometry, peak flows, quality of life score, medication usage, and symptoms. A convenience sample of 22 patients with moderate and severe-persistent asthma in the University of New Mexico Adult Asthma Clinic were evaluated during a routine clinic visit and then noted whether they had an exacerbation within 2 weeks of the initial appointment. Those with an exacerbation had a higher mean FeNO (29.67 ppb ± 14.48) compared to those who did not (12.92 ppb ± 5.17), p = 0.002. A nominal logistic regression model to determine those variables that predict asthma exacerbation found that FeNO was the only significant predictor, p = 0.03. Thus, FeNO appears to be a clinically useful tool to assess disease control in this population.     

An Evaluation of Standardizing Target Ventilation for Eucapnic Voluntary Hyperventilation Using FEV1

Athletes are required to provide objective documentation of exercise-induced bronchoconstriction (EIB) to use β₂-agonists during Olympic competition. A positive response to bronchial provocation by eucapnic voluntary hyperventilation (EVH) is considered acceptable confirmation of EIB. Thirty times forced expiratory volume in the first second (FEV₁) is recommended as EVH target ventilation (TV), an intensity intended to estimate 85% of maximal voluntary ventilation (MVV). There is a paucity of data examining the accuracy of predicting MVV from FEV₁ in elite athletes. The purpose of this study was to evaluate the efficacy of 30 × FEV₁ as standardized EVH TV. Maximal minute ventilation during exercise (VEmax) and pulmonary function of 78 elite winter athletes (25 males, 53 females; 25 EIB positive, 53 normal) were analyzed retrospectively. Adequacy and variability of the equation was ascertained by examining the ratio of EVH TV (30 × FEV₁) to VEmax. VEmax was 99 ± 11% of predicted MVV (35 × FEV₁) and was positively related (r = 0.85, p ≤ 0.05). TV was 88 ± 9% of VEmax (range: 64-109). For elite athletes, the high variability in 30 × FEV₁ to standardize TV for EVH may result in under-diagnosis for low-end outliers. Since VEmax of elite endurance athletes is typically known (via maximal aerobic testing) we recommend 85% VEmax as a more accurate and reliable method to establish EVH TV for this group; if VEmax is not available, then 85% of measured MVV may be used.     

Repeated inhalation of bradykinin attenuates adenosine 5'-monophosphate (AMP) induced bronchoconstriction in asthmatic airways.

Repeated bronchial challenges with inhaled bradykinin lead to a rapid loss of the bronchoconstrictor response and this has been suggested to be due to depletion of contractile neuropeptides from sensory nerve endings. If adenosine 5'-monophosphate (AMP), another potent bronchoprovocant in asthma, and bradykinin share a common pathway in inducing bronchoconstriction in asthmatic subjects, then repeated bradykinin bronchoprovocation tests should reduce the response to subsequent inhalation of AMP. We examined this hypothesis in eight asthmatic subjects in a double-blind, randomized study. On the histamine study day, two consecutive concentration-response studies with inhaled histamine were followed by a third consecutive challenge with AMP and the provocation concentration producing a 20% fall in forced expiratory volume in one second from the post-diluent baseline value (PC20 FEV1) for this agonist was calculated. On the bradykinin study day, two consecutive bronchoprovocation tests with bradykinin were followed by a third inhalation challenge to obtain the PC20AMP value. On a further occasion, the asthmatic subjects underwent two consecutive concentration-response studies with inhaled bradykinin followed by a third consecutive challenge with histamine. On the histamine study day, the geometric mean PC20AMP value was 28.1 mg.ml-1, whilst on the bradykinin study day, the fifteenfold reduction in bradykinin responsiveness after the second bradykinin challenge was accompanied by a significant reduction of the airway responsiveness to AMP, the PC20AMP being 59.8 mg.ml-1. A similar reduction in bradykinin responsiveness failed to alter the airway response to a subsequent inhalation with histamine.(ABSTRACT TRUNCATED AT 250 WORDS)