Role of small airways in asthma: investigation using high-resolution computed tomography

BACKGROUND: Small airways may have an important role in asthma but are more difficult to assess pathologically than central airways. Computed tomographic indices of lung density are assumed to reflect air trapping and may be a useful noninvasive measure of small airways disease, but their pathophysiological relevance remains undetermined. OBJECTIVE: To evaluate lung density on high-resolution computed tomography and examine its correlations with clinical and physiologic variables in 29 patients with stable asthma. METHODS: Both lungs were scanned at full-inspiratory and full-expiratory phases to quantify percentage of lung field occupied by low attenuation area (LAA%; < -960 Hounsfield units) and mean lung density. Asthma severity, pulmonary function, methacholine airway sensitivity and reactivity, and sputum eosinophil counts were evaluated. RESULTS: The mean lung density increased and LAA% decreased in all patients at expiratory phase compared with inspiratory phase. The inspiratory density indices and expiratory mean lung density correlated only with FEV(1)/forced vital capacity (FVC). Expiratory LAA% correlated more strongly than other variables with FEV(1)/FVC and with indices of peripheral airflow obstruction. Expiratory/inspiratory ratios of LAA% and mean lung density correlated, the former more strongly, with disease severity, residual volume/total lung capacity, and airway sensitivity, as well as with indices of global (FEV(1) and FEV(1)/FVC) and peripheral airflow obstruction. CONCLUSION: Expiratory/inspiratory high-resolution computed tomography is useful for assessing small airways disease in asthma. Small airways involvement is associated with airflow obstruction, airway hypersensitivity, and more severe disease. CLINICAL IMPLICATIONS: Small airways are an important therapeutic target in asthma.     

Isocapnic hyperventilation with cold air in healthy non-smokers, smokers and asthmatic subjects

Isocapnic hyperventilation with subfreezing air was performed by 15 healthy non-smokers, 10 asymptomatic smokers and 9 asthmatics. All subjects had normal ventilatory function and airway resistance (Raw) before challenge. The hyperventilation was performed twice. In one session, total respiratory resistance (Rrs) and reactance (Xrs) were measured at various frequencies, using a forced oscillation technique; in another session, vital capacity (VC), forced expiratory volume in 1 s (FEV1), maximal expiratory flow rates (FEF) and Raw were determined. In non-smokers, no changes in FEV1, FEF nor Raw were observed, whereas Rrs increased significantly (+ 20% of the prechallenge value), without change in resonant frequency nor in the Rrs-frequency relationship. This suggests a constrictory effect on central airways (possibly a narrowing of the glottis) only. In smokers, Rrs showed a similar, though longer lasting, increase than in non-smokers. Besides, a significant change of the Rrs-frequency relationship and a reduction in FEF at 50% of VC was found, suggesting an involvement of peripheral airways also. In asthmatics, bronchial reactivity was more pronounced, resulting in significant changes in all parameters: Rrs increased by about 100% of the prechallenge value, and became highly frequency dependent; Xrs decreased markedly, resulting in an increase in resonant frequency of the respiratory system. Similarly, VC, FEV1 and FEF decreased. These alterations are compatible with a more generalized constriction of the peripheral as well as central airways.     

Enhanced bronchial expression of extracellular matrix proteins in chronic obstructive pulmonary disease

Remodeling of airways and blood vessels is an important feature in chronic obstructive pulmonary disease (COPD). By using immunohistochemical analysis, we examined bronchial expression patterns of various extracellular matrix (ECM) components such as collagens (subtypes I, III, and IV), fibronectin, and laminin beta2 in patients with COPD (forced expiratory volume in 1 second [FEV1] or=85%; n = 16) and correlated expression data with lung function. Quantitative analysis revealed enhanced levels (P < .01) of total collagens I, III, and IV in surface epithelial basement membrane (SEBM) and collagens I and III in bronchial lamina propria (P < .02) and adventitia (P < .05) in COPD. Distinct and increased (P < .05) vascular expression of fibronectin accounts for intimal vascular fibrosis, whereas laminin beta2 (P < .05) was elevated in airway smooth muscle (ASM). FEV1 values inversely correlated with collagens in the SEBM, fibronectin in bronchial vessels, and laminin in the ASM. Our data suggest that COPD exhibits increased bronchial deposition of ECM proteins that contribute to deteriorated lung function and airway remodeling.     

支气管哮喘患者FeNO的表达及临床意义

目的:探讨不同呼出气一氧化氮(Fractional exhaled nitric oxide,FeNO)水平下支气管哮喘患者痰液、血液、肺功能检测等多个观察指标的表达特点,并分析在气道高反应性中的预测价值。方法:选取2017年1月至2019年5月于我院就诊的120例疑似支气管哮喘患者作为研究对象进行前瞻性分析,根据FeNO水平不同,将FeNO>49 ppb的42例患者列为高水平组,FeNO为26~49 ppb的33例患者为低水平组,FeNO≤25 ppb的45例患者为正常组。比较三组患者的基本临床资料、痰嗜酸性粒细胞、痰中性粒细胞、血嗜酸性粒细胞阳离子蛋白(Eosinophilic cationic protein,ECP)和免疫球蛋白E(Immunoglobulin E,IgE)以及第1s用力呼气容积(Forced expiratory volume at 1s,FEV1)、FEV1占预测值百分比(FEV1%Pred)、用力肺活量(Forced vital capacity,FVC)以及FEV1与FVC比值(FEV1/FVC)等肺功能检测结果进行统计分析。结果:经Spearman相关性分析显示,血IgE、ECP水平与FeNO水平呈正相关(r=0.615/0.629,P>0.01),FEV1%pred、FEV1/FVC与FeNO水平呈负相关(r=-0.494/0.789,P>0.01)。其中血IgE、ECP、FEV1%pred、FEV1/FVC对于预测支气管哮喘有一定的价值,而联合上述指标对于预测支气管哮喘的准确性最佳(AUC=0.920,P>0.01)。结论:不同FeNO水平支气管哮喘患者在临床表现中具有显著差异,在血IgE、ECP和肺功能FEV1%pred、FEV1/FVC指标检测的基础上增加FeNO可大大增加预测支气管哮喘的准确性。     

Airway function correlates with circulating eosinophil, but not mast cell, markers of inflammation in childhood asthma

Background Lung function tests, including forced expiratory volume in one second (FEV₁), forced expiratory flow at 25–75% of vital capacity (FEF_25–75%) and provocation concentrations of histamine which reduce FEV] by 20% (PC₂₀), are used as indicators of airway form and function in bronchial asthma. Recently, markers of eosinophil activation in bronchial lavage and serum have been suggested as a measure of eosinophil mediated inflammation in the airways. These include eosinophil cationic protein (ECP), eosinophil protein X (EPX) (also known as eosinophil derived neuro-toxin) and eosinophil peroxidase (EPO). Similarly, serum tryptase has been used as a marker of mast cell activation in systemic anaphylaxis. Objectives We measured both sets of indices in a group of children with moderately severe asthma to assess the contribution of eosinophil and mast cell mediated events to airflow limitation and bronchial hyperresponsiveness. Methods Forty-eight children aged 5–10 years had spirometric assessments, histamine challenges and blood sampling on the same occasion. After analysis of sera, the indices were compared. Results The eosinophil markers ECP and EPX correlated very well with each other. They showed a moderate negative correlation with PC₂₀ for histamine. EPX was also found to negatively correlate with FEV, and FEF_25–75%. Serum tryptase levels showed no such correlates with airway function. Conclusion These results suggest that serum markers of eosinophil activation correlate with airway function in childhood asthma, and may be of value in assessing the severity of the disease. It further supports the notion that childhood asthma has a similar immunopathology to that occurring in adults, with predominance of eosinophil mediated inflammation.     

Correlation of nasal inflammation and nasal airflow with forced expiratory volume in 1 second in patients with perennial allergic rhinitis and asthma.

BACKGROUND: Allergic rhinitis and asthma are frequently associated and are characterized by TH2-dependent inflammation. Nasal and bronchial obstruction largely depend on allergic inflammation. OBJECTIVE: To evaluate the relationships among nasal eosinophil counts, interleukin 4 (IL-4) and interferon-gamma (IFN-gamma) levels, nasal airflow, and forced expiratory volume in 1 second (FEV1) in patients with perennial allergic rhinitis and asthma. METHODS: Eight men and 7 women (mean +/- SD age, 24.8 +/- 4.7 years) with perennial allergic rhinitis and asthma were evaluated. All 15 patients had a moderate-to-severe grade of nasal obstruction. Total symptom score, rhinomanometry, nasal lavage, nasal scraping, and spirometry were evaluated in all patients. Eosinophils were counted using conventional staining; IL-4 and IFN-gamma levels were measured by immunoassay in fluids recovered from nasal lavage. RESULTS: Significant positive relationships were demonstrated between eosinophil infiltration and IL-4 levels, nasal airflow and IFN-gamma levels, FEV1 and IFN-gamma levels, and nasal airflow and FEV1 (P < .001 for all). Significant negative relationships were demonstrated between eosinophil infiltration and IFN-gamma levels, IL-4 and IFN-gamma levels, eosinophil infiltration and nasal airflow, IL-4 values and nasal airflow, nasal eosinophil counts and FEV1, and IL-4 values and FEV1 (P < .001 for all). CONCLUSIONS: There is a close association between TH2 cytokines and eosinophil infiltration in the nose. There is also clear evidence concerning the relationships among eosinophil infiltration, IL-4 and IFN-gamma levels, and nasal airflow. Nasal eosinophil, IL-4, and IFN-gamma levels correlate with FEV1. Finally, nasal airflow is related to FEV1. These findings constitute the first evidence of a relationship between TH2-related nasal inflammation and nasal and bronchial airflow in patients with perennial allergic rhinitis and asthma.     

The tendency to altered perception of airflow resistance in aged subjects might be due mainly to a reduction in diaphragmatic proprioception

Elderly patients with asthma, particularly those above the age of 80 years, appear less able to detect early worsening of their airflow resistance and hence might not take 'rescue' bronchodilator medication promptly. No consistent explanation for the observation has been posited. We hypothesize that deterioration in the sensitivity and accuracy of inspiratory (mainly diaphragmatic) proprioception is a plausible mechanism. This contention is supported by observations that indicate the central role of afferent phrenic nerve fibres arising from mechanoreceptors in diaphragmatic muscle and entheses in the ability to sense changes in intrathoracic pressure and volume. Other sensory afferent sources appear less important in this context because the ability to detect intrathoracic pressure and volume changes is preserved in patients with heart-lung transplants (parenchymal and airway denervation), topically anaesthetized upper airways and spinal cord transection below C4 (intact phrenic function) but not cord transection above C2 (phrenic function absent) if the airways are simultaneously anaesthetized. Further support for the hypothesis comes from demonstration of reduced integrated proprioceptive function in older subjects, such as increased postural sway, reduced ability to judge changes in joint position and slower recovery from eye and hand perturbation. In the context of asthma, the detection of a change in airflow resistance depends mainly on the subconscious detection of a mismatch between the inspiratory effort and the volume change achieved; the resulting discrepancy between length (volume) and tension (muscular effort) is felt as a sensation of obstructed breathing, resulting in greater effort to breath and conscious actions such as self-medication. Our hypothesis proposes that a reduced ability to detect accurately the volume change during tidal breathing delays the sensing of the obstruction in older subjects.     

Exercise-induced asthma: is it the right diagnosis in elite athletes?

Exercise-induced asthma, as recognized in asthmatic subjects, is an exaggerated airway response to airway dehydration in the presence of inflammatory cells and their mediators. The airway narrowing is primarily caused by contraction of bronchial smooth muscle. The milder airway narrowing documented in response to exercise in elite athletes and otherwise healthy subjects may simply be the result of the physiologic responses and pathologic changes in airway cells arising from dehydration injury. These changes, which include excessive mucus production and airway edema, would serve both to cause cough and to amplify the narrowing effects of normal bronchial smooth muscle contraction, resulting in symptoms. These changes are more likely to occur in healthy subjects who exercise intensely for long periods of time breathing cold air, dry air, or both. Under these conditions, the ability to humidify inspired air may be overwhelmed, causing significant dehydration of the airway mucosa and an increase in osmolarity, even in small airways. In addition to dehydration injury, airway narrowing to pharmacologic and physical agents may occur as a result of injury caused by large volumes of air containing irritant gases, particulate matter, or allergens being inspired during exercise. As a result, the airways may become inflamed, and the airway smooth muscle may become more sensitive. These events could result in the same exaggerated airway response to dehydration, as documented in asthmatic subjects.     

Influence of airways resistance on the nitrogen washout from the lung during forced rebreathing

The forced rebreathing method was used to determine the rate of change (apparent increase) of residual volume (RV) per breath in a group of 64 healthy non-smokers, 449 healthy smokers and 28 patients with chronic obstructive pulmonary disease (COPD). The mean FEV(1)% FVC in the patients was 48.28% (SD= = 8.9%). The rate of breathing into the bag-bottle system was maintained at 28 breaths per minute for all subjects. An asymptote in the nitrogen washout curve was reached within 5 breaths in healthy subjects as compared to between 7-13 in patients with COPD. The mean apparent increase in RV average 11ml/breath, 15ml/breath and 18ml/breath in healthy non-smokers, smokers and patients with COPD respectively. The mean apparent increase in RV in healthy non-smokers approximated a normal resting oxygen consumption per minute. It was higher in healthy smokers and patients with COPD than in healthy non-smokers. It is concluded that because of a high airway resistance, the forced rebreathing increases the work of breathing in order to overcome resistance to gas flow in the airways. More energy is required and oxygen is removed from the bag-bottle system without a corresponding replacement with carbon dioxide. The volume of the bag-bottle system progressively decreases resulting in a high apparent increase in RV.     

Airway function and nasal inflammation in seasonal allergic rhinitis and asthma

BACKGROUND: Allergic rhinitis (AR) and asthma are frequently associated and characterized by a Th2-dependent inflammation. Nasal and bronchial obstruction may be objectively measured. OBJECTIVE: The aim of this study was to evaluate the relationships among upper and lower airway function and nasal inflammation in subjects with seasonal allergic rhinitis (SAR) and asthma. METHODS: Twenty out-patients (12 males and eight females, mean age: 23.4+3.6 years) with SAR and asthma were evaluated during the pollen season. All of them showed a moderate-severe grade of nasal obstruction. Total symptom score, rhinomanometry, spirometry, nasal lavage, and nasal scraping were obtained in all subjects. Eosinophils were counted by conventional staining; IL-4 and IFN-gamma were measured by immunoassay on fluids recovered from nasal lavage. RESULTS: Functional parameters, i.e. nasal airflow and forced expiratory volume in 1 s (FEV(1)), were correlated with nasal eosinophils (R(2)>0.83, P<0.001). Inflammatory parameters, i.e. eosinophils were correlated with immunological parameters, i.e. IL-4 and IFN-gamma levels (R(2)=0.93, P<0.001). Nasal symptoms were correlated with nasal airflow (rho=-0.71, P< or =0.01) and eosinophils (rho=0.72, P<0.01). Nasal airflow was correlated with FEV(1) (r=0.89, P<0.0001). CONCLUSIONS: This study demonstrates the close connection between Th2 cytokines and eosinophil infiltration in the nose. There is also clear evidence concerning the relationships between eosinophils infiltration and cytokines levels. Nasal eosinophils can be regarded as the most important predictors of upper and lower airway functions. These findings constitute first evidence of a relationship among nasal Th2-related inflammation and nasal and bronchial airflow in patients with SAR and asthma.     

Nitrogen dead space in heavy smokers aged 44-58 years

Functional and alveolar dead spaces for nitrogen (VDF and VDalv) were calculated in a population of 20 male and 20 female heavy smokers and compared to data from static and forced spirometry (functional residual capacity [FRC], residual volume [RV], lung clearance index [LCI] and volume of trapped gas [VTG]) obtained with the same multiple-breath nitrogen wash-out as the dead spaces, and to variables considered sensitive to small airways disease measured with a single-breath nitrogen elimination (closing volume in per cent of vital capacity [CV%], closing capacity in per cent of total lung capacity [CC%] and slope index [SI]). Both nitrogen dead spaces increased with tidal volume in smokers as well as in healthy non-smokers. The majority of smokers were outside the predicted mean +2 SD for VTG (75%), CC and VDalv (70%) and SI (65%). The following variables were less sensitive for disclosing abnormality: CV (55%), RV (53%), LCI (38%) and forced expired volume in the first second (FEV1, 33%). If high sensitivity is considered preferable in epidemiological studies, the nitrogen dead spaces are equally as sensitive as the better of earlier described tests, and significantly superior to LCI and FEV1. Being tests that measure alveolar distribution of inhaled gas, they are probably sensitive to small airways disease.     

The changes in airway structure associated with reduced FEV1

The purpose of this study is to clarify the changes in the small airways associated with reduced forced expiratory volume in one second (FEV1). We compared the structure of the membranous and respiratory bronchioles of resected lungs from 111 patients with a normal predicted FEV1 to the structure of these airways from 45 patients with an FEV1 reduced below the 95% confidence limits for height and age. Membranous and respiratory bronchioles of less than 2 mm in internal diameter were counted and their diameter and wall thickness were measured. The data show that there were more membranous bronchioles of internal diameter less than 0.4 mm in patients with reduced FEV1. The walls of membranous bronchioles were not increased in thickness but there was an increase in the ratio of wall thickness to lumen diameter. The wall thickness of respiratory bronchioles was increased in the obstructed group and there was also an increase in the ratio of wall thickness to lumen diameter in these airways. We conclude that the patients with obstructive lung disease have a greater increase in wall thickness than can be explained by a reduction in airway support due to emphysema and suggest that the airways obstruction in these patients is due to thickening of the wall and narrowing of the lumen by a chronic inflammatory process.     

Morphometry of the human pulmonary acinus

The geometry and morphometry of intraacinar airways in human lungs were studied on silicone rubber casts from two adult lungs. We defined acini as the complex of alveolated airways distal to the terminal bronchioles--that is, beginning with the first-order respiratory or transitional bronchiole. The morphological properties of pulmonary acini are described. The acinar volume averages 187 mm3 (SD +/- 79 mm3). Intraacinar airways branch dichotomously over about 9 generations (range 6-12). The internal airway diameter falls from 500 micron to 270 micron between acinar generations 0 and 10, whereas the outer diameter (including the sleeve of alveoli) remains constant at 700 micron. Towards the periphery the size of alveoli increases and clusters of alveoli become more numerous. The longitudinal path length of acinar airways (defined as the distance along the ducts from the transitional bronchiole to the alveolar sacs) averages 8.8 mm (+/- 1.4 mm). The morphometric data collected in this study are used to construct an idealized model of human acinar airways that can be related to existing models of the human bronchial tree.     

Airway inflammation in asthma and chronic obstructive pulmonary disease with special emphasis on the antigen-presenting dendritic cell: influence of treatment with fluticasone propionate

Asthma is a chronic inflammatory disorder of the airways characterized by variable airflow limitation and airway hyperresponsiveness. The type of inflammatory response in asthma is compatible with a major contribution of professional antigen-presenting cells. The airways in chronic obstructive pulmonary disease (COPD) are also markedly inflamed; however, the predominant types of inflammatory cells and the main anatomical site of the lesion appear to differ from those in asthma. COPD is characterized by reduced maximum expiratory flow and slow forced emptying of the lungs. Steroids are the most prominent medication used in the treatment of asthma and COPD; however, the beneficial effect of steroid treatment in COPD is subject of debate. We investigated the efficacy of fluticasone propionate (FP) treatment in atopic asthmatics and in COPD patients with bronchial hyperreactivity who smoke. The effect of the treatment on bronchial hyperreactivity and indices of the methacholine dose–response curve were analysed, as well as indices of inflammation of the airway mucosa with special emphasis on the antigen presenting dendritic cell. Treatment of allergic asthmatic patients resulted in improvement of lung function (FEV₁), a decrease in bronchial hyperresponsiveness and a decrease of maximal airway narrowing. During the FP-treatment of COPD patients, FEV₁ remained stable, while FEV₁ deteriorated significantly in the placebo group. Therefore, steroid treatment may have a beneficial effect in COPD patients with bronchial hyperresponsiveness (BHR). Since immunohistochemical analysis of bronchial biopsy specimens from asthma and COPD patients show disease-specific aspects of inflammation, the anti-inflammatory effect of FP is obtained through modulation of different cell populations in asthma and COPD.     

Provoked models of asthma: what have we learnt?

Asthma is a chronic inflammatory disease of the airways characterized by physiological abnormalities of variable airflow obstruction and airway hyperresponsiveness (AHR) to a wide variety of physical and inhaled chemical stimuli and the presence of symptoms. AHR is measured by challenging the airways with a variety of agonists and naturally occurring stimuli, which results in constriction of the airway smooth muscle, leading to airway narrowing and airflow limitation. There are two distinct mechanisms by which the airways can narrow to a constrictor stimulus and these are defined by the pathways they take to induce AHR. Direct stimuli are pharmacological agents administered exogenously (such as histamine or methacholine) that act 'directly' on specific receptors on the bronchial smooth muscle to cause constriction. The other mechanism by which the airway can narrow is via the inhalation of indirect stimuli, which include natural stimuli, such as allergen or exercise, and pharmacological agents such as adenosine monophosphate and hyper-osmotic agents (e.g. hypertonic saline or dry powder mannitol). These stimuli induce airway narrowing 'indirectly' by causing the endogenous release of mediators of bronchoconstriction from airway inflammatory cells. Provoked models of asthma have been extremely valuable in understanding the pathobiology of asthma, in aiding diagnosis, in helping to clarify the mechanisms of actions of effective drugs and in the development of new entities to treat asthma. Some provoked models are valuable clinically, particularly those that measure direct AHR, while others, particularly allergen challenge, have been used in animal models and in humans to study the mechanisms of allergen-induced airway inflammation and the associated physiological changes, as well in the development of new drugs for asthma. An emerging role for measurements of AHR is in the evaluation of the optimal treatment for patients with asthma.     

Comparison of three normal breathing techniques to assess reversibility of airway obstruction.

Measurement of forced expiratory volume in one second (FEV1) is generally used to assess airway obstruction. Function tests during normal breathing are used as complementary tests as well as alternatives. Studies have been done comparing the esophageal pressure method with body plethysmography, and respiratory acoustical impedance with body plethysmography. We have not found any other studies comparing all three methods in the same subject. It is not clear whether those tests contribute to the assessment of reversibility of airways obstruction. We addressed the following questions: (1) How does the response of FEV1 to an inhaled beta agonist (400 micrograms fenoterol) relate to the response of lung function tests during normal breathing? (2) Are values obtained with three normal breathing techniques comparable in assessing severity of obstruction? We collected these data in 17 patients. A significant correlation was found between airway resistance measured with any of the three methods. The scatter was large, both before and after bronchodilation. The reversibility by the three methods expressed as absolute values (before and after inhalation) were comparable. In order of preference it appears that acoustical impedance is to be preferred to esophageal pressure because of less discomfort to the patient, and to body plethysmography because of the lower cost of the apparatus. Acoustical impedance can be used to assess acute changes in bronchomotor tone.     

Changes in airway dead space in response to methacholine provocation in normal subjects.

Measurements of bronchial hyper-responsiveness rely on sensitive techniques for measurement of bronchoconstriction, ideally based on tidal breathing. A potentially useful technique is measurement of airway dead space (VDaw), which reflects the volume of the conducting airways. The aim of this study was to evaluate measurements of VDaw with the single breath test for CO2 (SBT-CO2), compared to spirometric measurements, as a method of measuring bronchial response to methacholine challenge. Nineteen healthy adults were studied. Dosimetric methacholine challenge tests were performed on two study days. Forced expirations or the SBT-CO2 were used to assess the response. There were dose-dependent reductions in the spirometric measurements, with a 10 +/- 10% reduction from the baseline value of forced expiratory volume at the highest dose of methacholine. There was a dose-dependent reduction from the baseline value of VDaw by 19 +/- 9% at the highest dose. There was also a dose-dependent increase in the slope of the alveolar plateau of the SBT-CO2. This study provides support for measurement of VDaw as a means of evaluating bronchial responsiveness after methacholine challenge. In a group of healthy adults, this method shows a greater response but with similar dispersion as measurement of forced expiratory volume after methacholine challenge.     

Significance of area under the flow volume curve--useful index of bronchial asthma]

Some studies have reported that area under the flow volume curve (AUFVC) can be an index of pulmonary function. However, the significance of AUFVC remains to be clarified. We have clarified that AUFVC reflects the momentum of expired air. Size of flow volume curve (= AUFVC) has been commonly recognized to be changeable visually in patients with asthma. To clarify whether size of flow volume curve (= AUFVC) is a useful index of the course of bronchial asthma, we compared the rate of improvement forced expiratory volume in 1 second (FEV1.0), peak expiratory flow rate (PEFR) or forced vital capacity (FVC) to the rate of improvement in AUFVC after admission in 20 patients with bronchial asthma. The rate of improvement in AUFVC positively correlated with the rate of improvement in FEV1.0, PEFR or FVC. AUFVC demonstrated more marked improvement than other indices. Since AUFVC reflects the momentum of expired air, bronchial asthma's patients could understand visually that the momentum of expired air decreased due to airway stenosis by presenting flow volume curve. Therefore, visual size of flow volume curve helped patients with asthma to understand the condition of asthma. Size of flow volume curve (AUFVC) may be useful index of the course of bronchial asthma.     

Inhaled sodium fluoride decreases airway responsiveness to acetylcholine analogs in vivo

The study was conducted to characterize the action of NaF, which had relaxing property in carbachol precontracted isolated bovine bronchus, on airway responsiveness challenged by acetylcholine receptor agonists in rats and asthmatic humans.Tracheal flow rate and airway resistance were measured in anaesthetized rats. NaF was delivered either before carbachol challenge or together with carbachol. Patients with mild asthma were challenged with methacholine aerosol, and NaF was delivered when FEV1 fell by more than 20%. The results indicated that: (1) in rats NaF significantly inhibited carbachol-induced bronchial constriction when inhaled prior to carbachol challenge as airway resistances in the NaF and NaF+verapamil groups were significantly lower than those in the control group; (2) NaF significantly reversed carbachol or methacholine-induced bronchial constriction in asthmatic patients. In conclusion, NaF, delivered in form of aerosol, reduced bronchial responsiveness to carbachol in rats and had a bronchodilating effect on rat and human airways precontracted by inhalation of acetylcholine analogs.     

Bronchial response to acetylcholine and Dermatophagoides pteronissimus in asymptomatic asthmatics

Bronchial reactivity to increasing concentrations of acetylcholine (from 0.01 to 10 mg X ml-1) was studied in 84 asthmatic patients during a remission period. Three groups were identified based on decreasing reactivity : group 1 : 57 patients (68%) who exhibited a decrease equal or of more than 20% of forced expiratory volume per second (FEV1) and a decrease equal or of more than 35% of specific airway conductance (sGaw); group 2: 16 patients (19%) with a decrease in FEV1 of less than 20%, but a decrease in sGaw still equal or superior to 35%; group 3 : 11 patients (13%) with a less than 20% decrease in FEV1 and a less than 35% decrease of sGaw. Basal measurements of FEV1 and sGaw gave significantly lower values in group 1 than in group 2 and in group 2 than in group 3. A strong positive relationship was found between initial FEV1 (% of predicted) and acetylcholine concentration giving a fall of 20% in FEV1 (PD20-FEV1) (r = 0.87; p less than 0.001); a weak but still statistically significant relationship existed between initial sGaw and PD35-sGaw (r = 0.38; p less than 0.01). Twenty-five patients with allergic asthma were submitted to an inhalation test with Dermatophagoides pteronissimus (Dpt). Bronchial reactivity to Dpt was significantly correlated with acetylcholine (r = 0.9; p less than 0.001). Twenty-four hours after Dpt exposure, seven patients (28%) still presented bronchial obstruction. Eleven patients without persistent obstruction 24 h after Dpt exposure were resubmitted to acetylcholine; bronchial reactivity was found increased when compared to the initial acetylcholine-induced bronchospasm.(ABSTRACT TRUNCATED AT 250 WORDS)