Airway Eosinophilic Inflammation and Bronchial Hyperresponsiveness after Allergen Inhalation Challenge in Asthma

Allergen exposure in atopic asthmatic patients is associated with recruitment and activation of eosinophils in the airways. Once activated, eosinophils release toxic products, including the eosinophil cationic protein (ECP), able to damage bronchial structures and to increase bronchial hyperresponsiveness. With this background, the present study was designed to evaluate whether ECP levels in bronchoalveolar lavage (BAL) fluid could reflect, better than BAL eosinophil counts, the cellular activation that follows allergen exposure in atopic asthmatics. Twenty-two atopic patients attended the laboratory on two separate days. On the 1st day, they underwent methacholine (MCh) inhalation challenge to detect the degree of nonspecific bronchial hyperresponsiveness. On the 2nd day, they underwent fiberoptic bronchoscopy and BAL, at baseline or 4–6 h after allergen inhalation challenge. In this latter patient group, MCh challenge was repeated 3–5 h after allergen challenge, 1 h before fiberoptic bronchoscopy. The analysis of the mean baseline FEV₁ values and the degree of bronchial reactivity to MCh (MCh Pd₂₀) on the 1st study day did not demonstrate differences between the two patient groups (p > 0.1, each comparison). In addition, in the allergen-challenged group, MCh Pd₂₀ was decreased significantly after allergen challenge (151.4 μg/ml and 67.6 μg/ml, respectively, before and after challenge; p < 0.05). Evaluation of the different BAL cell types demonstrated that the proportions of eosinophils and epithelial cells were increased significantly in the allergen-challenged group compared with the group evaluated at baseline (p < 0.01 and p < 0.05, respectively). Moreover, ECP levels, corrected by the correspondent albumin levels (ECP/Alb), were higher in the allergen-challenged group compared with the group evaluated at baseline (p < 0.05). In addition, although a positive correlation was demonstrated between BAL eosinophil percentages and ECP/Alb values (r= 0.72, p < 0.05) in the group evaluated at baseline, no links were found between these parameters in the allergen-challenged group (p > 0.1). However, in this latter group, a weak positive correlation was demonstrated between eosinophil percentages and ΔMch, i.e., the increased nonspecific bronchial reactivity, which is observed after allergen challenge (r= 0.55; p < 0.05). Thus, in stable asthmatic patients an ongoing activation of eosinophils parallels their migration, but this eosinophilic inflammation is not strictly related to bronchial reactivity to Mch. By contrast, after allergen inhalation challenge, eosinophil recruitment and activation seem to follow different temporal kinetics, and eosinophilic inflammation may be partially associated with the degree of airway hyperresponsiveness. Accepted for publication: 15 September 1997     

Interaction of Vagal Lung Afferents with Inhalation of Histamine Aerosol in Anesthetized Dogs

In seven alpha-chloralose anesthetized dogs we examined the contribution of lung afferents to the rapid, shallow breathing induced by inhalation of 10 breaths of histamine aerosol. In four spontaneously breathing dogs, the inhalation of histamine caused an increased respiratory frequency, decreased tidal volume, and decreased dynamic lung compliance. Selective blockade of pulmonary C-fibers abolished a reflex-induced increase in respiratory frequency but did not significantly affect the reductions in tidal volume or lung compliance. Terbutaline treatment in combination with C-fiber blockade abolished the reductions in tidal volume and lung compliance induced by histamine. In three separate alpha-chloralose anesthetized, open-chest, mechanically ventilated dogs, we recorded an increase in the inspiratory activity of rapidly adapting pulmonary stretch receptors (RARs) induced by the inhalation of histamine aerosol. Selective C-fiber blockade abolished histamine-induced increases in RAR activity while only partially attenuating reductions in lung compliance. We conclude that the increase in RAR activity induced by histamine depends on intact C-fibers and not on a direct effect of histamine on RARs or an indirect effect of histamine reducing lung compliance. In addition, our data illustrate the multiple interactions that occur between the various vagal afferents and their roles in the reflexes induced by histamine inhalation. Accepted for publication: 2 December 1999     

Effects of GABA-B Agonist Baclofen on Bronchial Hyperreactivity to Inhaled Histamine in Subjects with Cervical Spinal Cord Injury

Bronchial provocation studies performed in our research center have consistently demonstrated airway hyperresponsiveness to both inhaled methacholine and histamine in subjects with chronic cervical spinal cord injury (SCI). More recently, we reported that the airways of such subjects maintained on chronic baclofen (γ-aminobutyric acid) therapy were not hyperreactive to inhaled methacholine. In this study we determined whether baclofen also blocks the effects of the bronchoprovocative agent histamine in subjects with cervical SCI. Twenty-four male subjects with cervical SCI participated in this study; 14 were maintained on oral baclofen, and 10 served as age-matched controls. The subjects were challenged with increasing concentrations of aerosolized histamine until either a 20% fall in forced expiratory volume in 1 s (FEV₁) from baseline (defined as PC₂₀) was observed, or a maximum of 25 mg/ml histamine was administered. We found that 11 of the 14 baclofen subjects (78.5%) and 8 of the 10 control subjects (80%) responded (PC₂₀ < 8 mg/ml) to the histamine challenge. Mean PC₂₀ values among responders in the baclofen (PC₂₀= 2.91 ± 2.3) and control (PC₂₀= 2.18 ± 1.9) groups did not differ significantly. Because histamine acts directly on histamine receptors and indirectly on cholinergic pathways, our findings that baclofen blocks bronchoconstriction due to inhaled methacholine, but not that due to histamine, suggests that hyperresponsiveness in subjects with cervical SCI may be secondary to nonspecific airway hyperreactivity. Accepted for publication 21 January 1997     

Long Term Cigarette Smoke Exposure Does Not Increase Airway Responsiveness in Rats

To ascertain whether chronic cigarette smoke exposure induces increased airway responsiveness, we performed methacholine response tests in Sprague-Dawley rats by calculating pulmonary resistance after nebulization of saline followed by an increasing concentration of methacholine. We also calculated the concentration of methacholine which doubled the baseline resistance (R200). Tests were performed at baseline and after 2, 4, 8, and 12 months of exposure to the smoke of seven cigarettes per day, 5 days each week; control animals were exposed to room air. At the completion of the study, there were 13 rats in the smoke-exposed group and 7 rats remaining in the control group. Airway morphology was assessed using a point counting technique. We found that (1) chronic exposure to cigarette smoke did not alter either the baseline resistance or the R200; (2) the saline baseline resistance decreased over time in the control animals; and (3) at the 12-month time point, smokers with increased baseline airway resistance had greater amounts of airway smooth muscle compared with the smoke-exposed animals without increased resistance. We conclude that in this animal model, long term exposure to cigarette smoke did not alter the response to methacholine but did increase airway smooth muscle and baseline resistance in some but not all animals. Accepted for publication: 4 December 1997     

Variability of Airway Responses in Mice

We examined the effect of animal strain, type of spasmogen, and mode of spasmogen administration on the pattern of lung mechanical responses in intubated and mechanically ventilated mice. We determined the response in inspiratory respiratory system resistance (R_rs) and inspiratory static respiratory system compliance (C_rs) to increasing doses of inhaled or intravenous carbachol or serotonin in Balb/C and C57BL/6 mice. R_rs responsiveness was quantitated by calculating, by interpolation, the inhaled spasmogen concentration (PC₁₅₀) and intravenous spasmogen dose (PD₁₅₀) causing an increase in R_rs to 150% of baseline. C_rs responsiveness was calculated similarly for a decrease in C_rs to 85% of baseline (PC₈₅ for inhaled and PD₈₅ for intravenous spasmogen). Baseline R_rs and C_rs were similar in all groups. R_rs responsiveness to inhaled and intravenous carbachol and serotonin tended to plateau and was not different in the two strains. In contrast, C_rs responses were variable and had a greater mean PC₈₅ for inhaled serotonin than carbachol in both strains and a greater fall in mean C_rs at PC₁₅₀ for carbachol in Balb/C mice; no interstrain and interdrug differences in PD₈₅ were noted for intravenous spasmogens. Intravenous atropine attenuated the R_rs response to high-dose inhaled and intravenous serotonin, suggesting the involvement of a vagal reflex. In contrast, atropine attenuated C_rs responses only for intravenous serotonin in Balb/C mice. These results suggest that animal strain, spasmogen, and mode of administration determine the extent to which induced airflow resistance is accompanied by increases in elastic recoil. Accepted for publication: 24 June 1999     

Mediators and Oxygen Radicals in Hyperpnea-Induced Airway Constriction of Guinea Pigs

Leukotrienes (LTs), tachykinins (TKs), and oxygen radicals have been suggested to be important modulating factors for the hyperpnea-induced bronchoconstriction (HIB) of guinea pigs. In this study, we tested the hypothesis that LTs and oxygen radicals modulate HIB by triggering TK release. Eighty-five Hartley guinea pigs were divided into four groups: control, dimethylthiourea (DMTU), FPL 55712, and A63162. DMTU is the scavenger for hydroxyl radical. FPL 55712 is an antagonist of LT receptor, whereas A63162 is an inhibitor of lipoxygenase. Each group was further divided into three subgroups: baseline, hyperpnea, and recovery. Each animal was anesthetized, cannulated, paralyzed, and artificially ventilated. We measured dynamic respiratory compliance (Crs), maximal expiratory flow at 50% total lung capacity (V_max50), and forced expiratory volume in 0.1 s (FEV_0.1) during the baseline and recovery periods. Hyperpnea caused significant decreases in Crs, V_max50, and FEV_0.1, indicating HIB in the control group. Pretreatment with DMTU, FPL 5712, or A63162 attenuated HIB. Plasma substance P (SP) levels increased progressively during the experiment in all groups. However, both FPL 55712 and A63162, but not DMTU, significantly decreased SP levels. Similarly, lung malondialdehyde (MDA) contents increased progressively during the experiment in the control group. Neither FPL 55712 nor A63162 significantly affected the increase. On the contrary, DMTU significantly attenuated the increase in MDA during the recovery period. These results suggest that inhibition of LTs leads to suppression at SP levels and HIB, whereas DMTU attenuates HIB by means of other mechanisms. Accepted for publication: 25 April 2000     

Ebselen Decreases Ozone-Induced Pulmonary Inflammation in Rats

We studied the effects of ebselen on rat lung inflammatory responses against ozone exposure. Rats were treated with ebselen every 12 h from 1 h before a single 4-h exposure to 2 ppm ozone. Treatment with ebselen (10 mg/kg) significantly decreased pulmonary inflammation as indicated by the albumin concentration and the number of neutrophils in the bronchoalveolar lavage fluid 18 h after the ozone exposure. Although treatment with ebselen did not alter the macrophage expression of inducible nitric oxide synthase after the ozone exposure, it did markedly inhibit the nitration reaction of tyrosine residues, suggesting that ebselen scavenges peroxynitrite during ozone-induced pulmonary inflammation. Treatment with ebselen also enhanced the pulmonary expression of both copper, zinc, and manganous superoxide dismutases at the same time point. These enzymes may also contribute to a decrease in the formation of peroxynitrite by lowering the concentration of superoxide. Thus, ebselen represents a useful compound for protecting against certain acute lung injuries by modulating the oxidant-related inflammatory process. Accepted for publication: 8 May 2000     

Modulation of Airway Responsiveness to Acetylcholine by Nitric Oxide in a Rabbit Model

Nitric oxide (NO) is an important mediator in the regulation of bronchial muscle tone and airway responsiveness. We investigated the influence of exogenous NO on airway responsiveness to acetylcholine aerosols (ACH) in normal and in hyperresponsive rabbits. White New Zealand rabbits were anesthetized, intubated, and breathed room air spontaneously. Responses of respiratory parameters in ACH challenge tests were measured. In group A the influence of NO on ACH infusion-induced airway constriction was measured. Airway responses to aerosols from 0.25 to 8.0% ACH solutions in saline were measured with 150 and 300 ppm NO inhalation (groups B and C) and compared with the same animals' responses without NO. Moreover, we examined the influence of NO synthase inhibition on airway responsiveness (group D) and the modulatory effect of NO in hyperresponsive animals (group E). 300 ppm NO inhalation significantly decreased the bronchoconstrictor response to intravenously administered ACH (group A). However, the baseline value of dynamic elastance (E_dyn) was only marginally lower under the influence of 300 ppm NO. During inhalation of 150 or 300 ppm NO, responses to nebulized 2.0% and less ACH solutions remained nearly unaltered. Responses to aerosols of 4.0 and 8.0% diminished significantly (groups B and C). Following 40 min of aerosolized N-nitro-l-arginine-methyl ester (l-NAME) solution (a NO synthase inhibitor, 1.2 mM) inhalation, the response of E_dyn to ACH increased significantly in group D. In group E, animals inhaled 500 mg/m³ ammonium persulfate (APS), an oxidant with various industrial applications, after the first ACH challenge test (0.2, 1.0, and 2.0% ACH). After 2 h of APS exposure, the ACH-induced broncho constriction was increased significantly in the challenge test. After another 2 h of APS inhalation, the airway responsiveness to ACH was tested under the influence of 300 ppm NO. NO significantly decreased the response to ACH to almost the same level as before APS exposure. The results indicate that responses to high ACH concentrations as well as an APS-induced increase in ACH responsiveness were effectively reduced by high concentrations of inhaled NO. Accepted for publication: 11 February 1997     

The Importance of Polymorphonuclear Leukocytes in Lipopolysaccharide-Induced Superoxide Anion Production and Lung Injury: Ex Vivo Observation in Rat Lungs

The purpose of this study is to determine if the polymorphonuclear leukocyte (PMN) is a major causative agent for lipopolysaccharide (LPS)-induced lung injury and responsible for the excess production of superoxide anion in the lung. We measured superoxide anion production from the lung and pulmonary capillary permeability in rats with and without PMN depletion. The superoxide anion production from the lung was measured using a purpose-built ex vivo chemiluminescence apparatus. Pulmonary capillary permeability was evaluated by the Evans blue dye extravasation method. PMN sequestration was determined by counting PMNs in histologic tissue specimens using microscopy. All rats received 3 mg/kg LPS intravenously. Examinations were undertaken at 2, 6, and 12 h after the LPS injection. The PMN-depleted group received cyclophosphamide 4 days before the LPS injection, which resulted in a PMN count of less than 200 cells/μl. In rats without PMN depletion, Evans blue dye extravasation increased significantly at 12 h after the LPS injection; PMN sequestration increased at 2, 6, and 12 h after the LPS injection; and superoxide anion production increased at 6 h and remained elevated at 12 h after the LPS injection. The increased permeability, PMN sequestration, and superoxide anion production were not seen in the PMN-depleted group. The contribution of the xanthine/xanthine oxidase system and alveolar macrophages to the observed superoxide anion production was negligible. We conclude that, in rats, the PMN is a major causative agent in LPS-induced lung injury and is responsible for the excess production of superoxide anion in the lung. Accepted for publication: 3 March 1997     

Bronchial Hyperresponsiveness in Farmers: Relation to Respiratory Symptoms, Lung Function, and Atopy

There is only limited information on the factors associated with nonspecific bronchial hyperresponsiveness (BHR) in farmers. Our purpose was to examine the relationship between BHR and respiratory symptoms, atopy, and abnormalities of lung function in a sample of French farmers. Farmers scheduled for a preventive medicine check-up in northeastern France were examined. Occupational exposure, respiratory symptoms, and work-related symptoms were assessed by questionnaire, sensitization to 34 common and agricultural allergens by skin prick tests, and BHR by the single-dose (1,200 μg) acetylcholine (ACh) challenge test. Data were obtained from 741 farmers (95% of those invited). Seventy-seven subjects (10.3%) had BHR defined as a fall in forced expiratory volume in 1 s (FEV₁) ≥ 10% after the inhalation of ACh or, for those with a poor lung function, an increase in FEV₁ > 10% and > 200 ml after the inhalation of 200 μg of salbutamol. The proportion of asthmalike symptoms, especially wheeze during work, positive skin tests to acarian (storage mites) and cereal dust allergens, and low levels of lung function was significantly greater among reactors than among nonreactors. Stepwise logistic regression analysis showed a significant and independent association between BHR and wheezing during work (OR = 4.99; 95% CI = 2.29–10.89; p= 0.0001) and baseline FEV₁ (OR = 1.49; 95% CI = 1.05–2.20; p= 0.026). In conclusion, hyperreactive farmers had significantly more asthmalike symptoms, positive skin tests, and abnormal lung function than normoreactive farmers. Work-related wheeze and low baseline FEV₁ were significantly and independently associated with BHR. Accepted for publication: 26 January 1999     

Basis of Rise in Intracellular Sodium in Airway Hyperresponsiveness and Asthma

The aim of this study was to investigate the basis of disturbances in sodium transport in asthma and in airway hyperresponsiveness without symptoms of asthma (asymptomatic AHR). We measured the intracellular sodium (Na_i); activity of Na⁺/K⁺-ATPase in unstimulated cells (resting activity) and in cell homogenate under optimal conditions (maximal activity); and sodium influx, in mixed leukocytes of 15 normal subjects, 12 subjects with asymptomatic AHR, and 26 asthmatics with or without active symptoms. Resting Na⁺/K⁺-ATPase activity was the same as sodium influx, consistent with homeostasis. Compared with normal subjects, those with asymptomatic AHR or asthma with controlled symptoms had a twofold increase in sodium influx and Na_i. Symptomatic asthmatics also had a twofold increase in sodium influx but a fourfold elevation of Na_i. Maximal Na⁺/K⁺-ATPase activity was reduced by half in symptomatic asthmatics compared with normal subjects. The reduction of maximal Na⁺/K⁺-ATPase activity was associated with a significant decrease in ATP turnover per Na⁺/K⁺-ATPase molecule but not number of Na⁺/K⁺-ATPase molecules per cell. In summary, airway hyperresponsiveness with or without asthma is associated with increased sodium influx and Na in leukocytes. Resting activity of Na⁺/K⁺-ATPase is also increased as a compensatory response to the increased sodium influx, but it is achieved at the expense of higher Na_i. Symptomatic asthma is additionally associated with reduction in maximal activity of Na⁺/K⁺-ATPase, resulting in reduced capacity to handle the increase in sodium influx and consequent severe elevations in Na_i.     

A Murine Model of Latex Allergy-Induced Airway Hyperreactivity

Sensitization to latex proteins can cause immediate IgE mast cell-mediated reactions. Health care workers have been found to be particularly at risk because of high exposure. Latex allergy can be produced in mice as demonstrated by IgE and eosinophil responses. Thus the mouse is a potential animal model for studying this disease, but the airway response to latex sensitization in mice has not been evaluated previously. In the present study, we immunized BALB/c mice intranasally with nonammoniated latex proteins. Animals were anesthetized, and lung mechanics were evaluated plethysmographically. Changes in pulmonary conductance (G_L) and compliance (C_dyn) were measured in response to a nonspecific challenge with methacholine or to a direct challenge with intravenous latex antigen. Latex sensitization resulted in elevated levels of IgE and latex-specific IgG₁ as well as interstitial infiltrates consistent with an allergic response. The methacholine dose-response ED₅₀ for G_L was 116.4 μg for the control mice and fell significantly to 20.9 μg for latex-sensitized mice. The ED₅₀ calculated for C_dyn was also significantly lower after latex sensitization. The G_L in latex-sensitized mice challenged with latex antigen fell significantly from a prechallenge value of 1.87 ± 0.41 (S.E.) to 0.198 ± 0.03 ml · s⁻¹· cmH₂O after latex antigen challenge. The results indicate that latex-sensitized mice did exhibit increased airway reactivity in the methacholine challenge test. The latex allergic response in mice is unique in that direct challenge with latex antigen itself also resulted in a significant airway response. Accepted for publication: 10 September 1998     

Age and Bronchial Hyperresponsiveness Are Associated with Failure to Perform the Single Breath N2 Test in a Rural Female Population

Because some authors have reported high rates of failure in performing the single breath N₂ (SBN₂) test in rural areas, the present study aimed at evaluating its acceptability in a female population, unfamiliar with lung function testing, in a rural area of northeastern France. Two hundred ninety-eight women from a rural area volunteered for a preventive medicine examination (91.6% of those invited); four of them were excluded for clinical reasons, and six (2%) were unable to perform spirometry. The protocol included completion of a questionnaire, spirometry with a bronchial reactivity test, skin prick test, and the SBN₂ test utilizing a computerized assembly. Although failures caused by the apparatus were few (n= 7, 2.4%) 96 of 281 women (34.1%) were unable to produce two valid SBN₂ tests in a series of six attempts. Compared with the group who succeeded in the test (n= 185), women who failed were older and had a higher prevalence of bronchial hyperresponsiveness. Logistic regression confirmed the independent association of these two variables with an inability to perform. We conclude that in a female population completely unfamiliar with lung function testing the SBN₂ test has a high rate of failure associated with higher age and the presence of bronchial hyperresponsiveness. Accepted for publication: 17 November 1998     

Glutathione Synthetic Activity in the Lungs in Newborn Guinea Pigs

Depletion of glutathione, a key antioxidant, accelerates lung injury. Glutathione concentrations are reduced significantly in premature infants with respiratory distress syndrome, leaving them at greater risk of bronchopulmonary dysplasia. A study was designed to verify if the increased glutathione synthetic activity observed in oxygen-dependent and ventilated newborn infants was caused by their postsurgical state. Our objective was to evaluate the role of a general surgical procedure as a factor affecting lung glutathione. One-day-old guinea pig pups, a well characterized animal model for the study of neonatal lung disease, were divided between those undergoing a standardized surgical procedure and those that did not. The pups were fed by their mother. After 4 days the lungs were sampled to determine total glutathione content, activities of γ-glutamyltranspeptidase, glutathione peroxidase, and reductase as well as the glutathione synthetic activity. The surgical procedure was associated with a specific stimulatory effect limited to glutathione synthetic activity (p < 0.02) leading to an increased (p < 0.02) pulmonary glutathione content. Glutathione concentration was significantly correlated (r ²= 0.67) with the synthetic activity. We concluded that in this animal model an invasive procedure such as a general surgical procedure affects lung glutathione metabolism in a fashion similar to that of hyperoxia. In the lungs, the synthetic activity is a stronger determinant of glutathione concentrations than the activities of the other enzymes involved in maintaining glutathione levels. Accepted for publication: 21 May 1998     

Effects of Age, Gender, Disease, and Multisystem Involvement on Oxygen Saturation Levels in Dysphagic Persons

The purpose of this study was to examine the effects of age, gender, disease, and multisystem involvement on SpO₂ levels of 104 dysphagic patients and 77 nondysphagic persons. Results indicated that solid aspirators had lower SpO₂ levels than liquid aspirators, penetrators, and nondysphagics. In addition, SpO₂ levels varied by age, with older persons having lower levels than younger persons among dysphagics but not among nondysphagics. Patients with COPD had lower SpO₂ levels than dysphagics with other disorders. Significant interactions were found among age, gender, and disease. Multisystem involvement was found not to be a factor in SpO₂ levels. It was concluded that although normal aging processes reduce swallowing and pulmonary functioning, it became a significant factor only when combined with an assault to the system, such as CVA or COPD.     

Byssinosis: Role of Polymer Length on the Effect of Tannin on the Airway β-Adrenergic Receptor

Tannin, isolated from cotton bracts and implicated in the pathogenesis of byssinosis, inhibits isoproterenol and forskolin-stimulated cAMP release from airway cells in part by decreasing cell surface β-adrenergic receptor number and uncoupling the β-adrenergic receptor from its stimulatory G-protein (G_s) and in part by inhibiting adenylyl cyclase activity. We have hypothesized that cotton tannin, because of its long polymer length, interacts with the hydrophobic binding pocket of the β-adrenergic receptor and alters β-adrenergic receptor binding and G_s coupling. In these studies, tannins of three different polymer lengths and molecular masses were isolated from cotton bracts using sequential Amicon ultrafiltration [molecular mass > 10,000 (YM10 retentate), 1,000–10,000 (YM10 filtrate), and 1,000–5,000 Da (YM2 retentate)]. The YM10 retentate (25 μg/ml) decreased chloride secretion (Jnet = 1.11 ± 0.28 (control) to 0.59 ± 0.18 μEq/cm²·h, p < 0.05, n= 6), decreased cell surface β-adrenergic receptor number (18.0 ± 1.8 (control) to 10.6 ± 0.9 fmol/mg protein, p < 0.02, n= 4), and inhibited forskolin-stimulated cAMP release (5,254 ± 1,290 (control) to 2,968 ± 620 pmol/mg protein, p < 0.01, n= 8). In contrast, neither the YM10 filtrate nor the YM2 retentate had any effect on net chloride secretion, β-adrenergic cell surface receptor number, or forskolin-stimulated cAMP release. We conclude that polymer length is essential for the effect of tannin on the β-adrenergic receptor and on adenylyl cyclase. Accepted for publication: 28 June 1998     

Lack of Correlation between Nonspecific Nasal and Bronchial Reactivity in Allergic Rhinitis Subjects

A link between allergic rhinitis and asthma has long been suspected, allergic rhinitis being considered a precursor of asthma. The hypothesis is that if such a link exists, then nonspecific nasal and bronchial reactivity are already correlated in acute rhinitis patients. To test for this correlation, we compared nonspecific nasal and bronchial reactivity in two groups of rhinitis subjects: 37 rhinitis pollinosis patients tested during the pollen season and 35 rhinitis pollinosis patients tested outside the pollen season. We also assessed how smoking affects this link. In each subject, allergy, nonspecific nasal, and nonspecific bronchial reactivity were tested, and smoking was categorized. We found no correlation between nonspecific nasal and bronchial reactivity in the two nonasthmatic rhinitis groups. During active allergic inflammation (pollinosis season) no shift toward a stronger link between upper and lower airways can be found compared with the latent period (out of pollinosis season). Unexpectedly, among smokers we found a significant relationship between nonspecific nasal and bronchial reactivity. Thus, there is not yet sufficient evidence for a straightforward link between nasal and bronchial hyperreactivity in nonasthmatic pollinosis rhinitis subjects. The development of asthma seems to be crucial for this link. Accepted for publication: 30 November 1998     

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.