Bronchoalveolar lavage does not alter airway responsiveness in asthmatic subjects

Bronchoalveolar lavage (BAL) during fiberoptic bronchoscopy is being used increasingly for the investigation of asthma. Airway responsiveness to methacholine is a sensitive indicator of the presence and severity of asthma. Therefore, we studied the effect of BAL on methacholine airway responsiveness in stable asthmatics. Geometric mean methacholine PC20 was 1.34 mg/ml before and 1.80 mg/ml after BAL (p = 0.26) in asthmatics. Immediate symptoms of airway narrowing after BAL occurred only in the 3 asthmatics with moderate to severe hyperresponsiveness. These symptoms were rapidly relieved by inhaled bronchodilator. There was no relationship between the occurrence of symptoms and the amount of topical lidocaine used for local anaesthesia or the volume of lavage fluid returned. The absence of an effect of BAL on airway responsiveness supports the safety of this procedure in the controlled asthmatic patient with near normal FEV1, irrespective of the level of baseline airway responsiveness.     

Bronchoalveolar lavage fluid from asthmatic subjects is mitogenic for human airway smooth muscle

Airway smooth muscle proliferation may contribute to the airway wall remodeling seen in asthma. In this study we tested for the presence of airway smooth muscle mitogenic activity in bronchoalveolar lavage (BAL) fluid obtained from 12 atopic asthmatics before and serially after segmental allergen challenge, and from four normal subjects who did not undergo allergen challenge. Mitogenic effect was assessed by coincubating BAL fluid with human airway smooth muscle cells, and measuring its effect on (3)[H]thymidine incorporation and cell number. Induction of ERK phosphorylation and cyclin D(1) protein abundance were also assessed. Compared with serum-free medium alone, BAL fluid obtained from normal subjects increased thymidine incorporation, cell number, ERK phosphorylation, and cyclin D(1) abundance. BAL fluid from asthmatic subjects prior to allergen challenge induced even greater increases in all measures, except for cell number, which was similar to that observed with normal subjects' BAL fluid. Incubation with lavage fluid obtained 48 h after segmental allergen challenge in atopic asthmatics caused yet further increases in thymidine incorporation, cell number, and cyclin D(1) protein abundance. Molecular sieving of prechallenge BAL fluid from three asthmatic subjects demonstrated that mitogenic activity was present exclusively in the > 10 kD fraction. These results provide the first direct demonstration that fluid lining the airways of asthmatics contains excess mitogenic activity for human airway smooth muscle, and that this activity increases further after allergen challenge.     

Platelet-activating factor in bronchoalveolar lavage fluid from asthmatic subjects

Bronchoalveolar lavage (BAL) was performed on 28 asthma patients, 7 patients with emphysema and 11 control subjects. Total and differential cell counts were performed and cellular metabolic activity was assessed using luminol and lucigenin amplified chemiluminescence. BAL supernatants were assayed for platelet-activating factor (PAF) and lyso-PAF using a sensitive guinea-pig bioassay. Eight of the asthma patients but none of the emphysema patients or control subjects had PAF in their BAL fluid. Lyso-PAF was measurable in BAL fluid in most subjects and no differences were detected between groups. Among the asthma patients, the presence of PAF in BAL supernatant was significantly associated with a combination of low neutrophil and high lymphocyte counts (p less than 0.05) and with macrophage metabolic activity as assessed by lucigenin chemiluminescence (p less than 0.05).     

Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs. Description of the model and local airway inflammation

The local mechanisms that result in the cellular inflammation and bronchial airway hyperreactivity that characterize allergic bronchial asthma are poorly defined. In order to study these processes, we developed a method for local allergen challenge using a fiberoptic bronchoscope and direct observation and bronchoalveolar lavage (BAL) to assess the airway responses to allergen. In these studies, 11 allergic asthmatics (all of whom had previously demonstrated a late-phase asthmatic response to aeroallergen challenge) and 6 healthy, asymptomatic subjects volunteered to undergo bronchoalveolar lavage after local airway challenge via a bronchoscope wedged into subsegmental airways. These studies revealed that asthmatic airways respond to allergen with an immediate pallor followed by reactive hyperemia, edema, and bronchial narrowing. This site and a control site were relavaged at 48 or 96 h after the immediate response. Neutrophils and eosinophils increased significantly at 48 h after challenge, as did helper T-lymphocytes. Characteristically, at 96 h, neutrophil counts returned to normal values, whereas eosinophiles and helper T-cells remained elevated. Peroxidase-staining cells were also elevated at 48 h after local allergen challenge. Electron microscopy revealed degranulation of mast cells and eosinophils, both immediately and later (48 and 96 h) after local allergen challenge. Macrophages were highly activated and had phagocytized, partially intact granules from both eosinophils and mast cells. There was a significant correlation (p less than 0.001) between the concentration of allergen required to produce a visible airway response and a positive end-point skin titration in the asthmatic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Leukocytes and mediators in bronchoalveolar lavage during allergen-induced late-phase asthmatic reactions

We have measured the total and differential cell counts, histamine, leukotriene (LT) B4 and LTC4, immunoglobulins, complement (C3), eosinophil-derived basic proteins, and monocyte complement rosettes in bronchoalveolar lavage (BAL) 6 h after challenge with either antigen or diluent control in seven patients with antigen-induced single early reactions, and seven with dual (early and late phase) reactions. In both groups, the total cell counts in BAL were similar, irrespective of whether they were challenged with antigen or diluent. However, in the late-phase responders (LPR), there were significant increases in lymphocytes, neutrophils, and eosinophils (p less than 0.05), and significant decreases in the percentage of lung mast cells (p less than 0.05). The eosinophil major basic protein and eosinophil-derived neurotoxin increased in four of five subjects with dual responses and in the majority of single early responders (SER). BAL histamine concentrations increased in five of seven patients with dual responses. There were no consistent changes in LTB4 concentrations in either the LPR or the SER between diluent and antigen days, but a small but significant increase in LTC4 was observed in the LPR. Concentrations of IgG, IgA, IgM, IgE, C3, and albumin did not differ significantly. The percentage of monocyte complement rosettes also increased significantly (p less than 0.05) in LPR, but not in SER. These findings support the hypothesis that eosinophils and their products play a role in tissue injury in LPR and that eosinophil infiltration may be associated with macrophage activation.     

The origin of water and urea sampled at bronchoalveolar lavage in asthmatic and control subjects.

Bronchoalveolar lavage (BAL) urea has been advocated as a denominator that might allow for the dilution of the pulmonary epithelial lining fluid sampled at BAL, and so provide a meaningful method of expressing BAL data. We investigated the origin of water and urea sampled at BAL in five asthmatic and five control subjects using radiolabeled urea injected intravenously 5 min before BAL. Labeled BAL urea was found to be fully equilibrated with that in the bloodstream. A strong relationship was found between influx of radiolabeled water and radiolabeled urea from blood to BAL fluid, suggesting that urea sampled at BAL may be derived predominantly from an acute movement from the bloodstream into the BAL aspirate. We conclude that urea is an inappropriate denominator for the expression of BAL results, and that the fluid and solute dynamics that occur during BAL are both complex and variable.     

Lack of airway response to nasal irritation in normal and asthmatic subjects

Abstract Twenty two subjects (10 normals, nine asthmatics and three who had suggestive histories for asthma but normal bronchial histamine challenges) underwent nasal challenges with logarithmic incremental doses of histamine or saline on alternate days. Nasal resistance (measured by posterior rhinometry), and forced expiratory volume in one second (FEV₁) were assessed after each dose of nasal histamine or placebo. After each nasal challenge (maximum nasal dose of 250 μg of histamine or doubling of nasal resistance) bronchial responsiveness was measured with a bronchial histamine challenge. Despite significant changes in nasal resistance with nasal histamine (p < 0.01) there was no significant change in the forced expiratory volume in one second, or in bronchial responsiveness. We were unable to demonstrate nasobronchial reflexes initiated by acute irritation of the nasal mucosa with histamine in either normal subjects or in those with mild to moderate asthma.     

Tissue inhibitor of metalloproteinase-1 levels in bronchoalveolar lavage fluid from asthmatic subjects.

Airway remodeling is a well-recognized feature in patients with chronic asthma. The accumulation in the submucosa of fibrous proteins that are substrates of matrix metalloproteinases (MMP), and the demonstration of increased levels of MMP-9 in bronchoalveolar lavage fluid, prompted us to determine whether there was an imbalance between MMPs and tissue inhibitors of metalloproteinase (TIMP) in such patients. We investigated the presence of TIMPs and other MMPs. TIMP levels were compared with those of all MMPs and inflammatory cytokines. Adults with stable asthma, either untreated or treated with glucocorticoids (GCs), were enrolled. Healthy nonsmokers served as a control population. MMPs and TIMPs were identified through zymography or immunoblotting. TIMPs, MMPs, and cytokines were measured with enzyme immunoassays. TIMP-1 levels were significantly higher in untreated asthmatic subjects than in GC-treated subjects or controls (p < 0.0001), and were far greater than those of MMP-1, MMP-2, MMP-3, and MMP-9 combined. TIMP-2 was undetectable. TIMP-1 levels were correlated with levels of interleukin-6 (p < 0.012) and the number of alveolar macrophages recovered (p < 0.005). This observation has important implications, since an excess of TIMP-1 could lead to airway fibrosis, a hallmark of airway remodelling in patients with chronic asthma.     

Role of chemical mediators in airway hyperresponsiveness in an asthmatic model

BACKGROUND: Airway hyperresponsiveness (AHR) is one of the characteristic features of human asthma. The presence of AHR and the precise mechanisms immediately after establishment of sensitization in guinea pigs are unclear, although there are many reports showing allergen exposure that causes an increase in bronchial responsiveness associated with eosinophil influx into the airway in sensitized guinea pigs. OBJECTIVE: We investigated the inhibitory effects on AHR to histamine of ONO-1078, a leukotriene antagonist; indomethacin, a cyclooxygenase inhibitor; S-145, a thromboxane A(2) (TXA(2)) antagonist, and Y-24180, a platelet-activating factor (PAF) antagonist, to assess the involvement of chemical mediators in AHR employing ovalbumin (OA) sensitized guinea pig models. METHODS: Male Hartley guinea pigs were used. Each group comprised 4-7 animals. The animals were sensitized to OA, injecting intraperitoneally 30 mg of cyclophosphamide and 2,000 microg of OA together with 100 mg of aluminum hydroxide as the adjuvant. The guinea pigs were artificially ventilated via a cannula using a small-animal respirator after intraperitoneal anesthesia with pentobarbital sodium for tracheotomy. The pressure at the airway opening (PAO) was measured using a differential pressure transducer, and a differential pressure of peak PAO (peak DeltaPAO) at inspiratory phase as an overall index of bronchial response to bronchoactive agents was used. While being artificially ventilated, the animals were exposed to physiological saline solution containing various concentrations of histamine (4.9, 9.8, 20, 39, 78, and 156 microg/ml) by inhalation for 30 s at 3-min intervals. Determinations were made at 1 min after each inhalation. The chemical mediators were each (30 mg/kg of ONO-1078, 3 mg/kg of S-1452, and 1 mg/kg of Y-24180) administered orally to sensitized guinea pigs, and the airway response to histamine was assessed. Each group comprised 4-7 animals. RESULTS: The airway response to histamine was significantly greater in the sensitized group than in the nonsensitized group at histamine concentrations of 36 (p < 0.05), 78, and 156 mg/ml (p < 0.01). Leukotrienes C(4) and D(4): 30 mg/kg of ONO-178 did not show any inhibitory effect on airway response to inhaled histamine. Cyclooxygenase: 5 mg/kg of indomethacin did not show any inhibitory effect on the airway response to inhaled histamine. TXA(2): the AHR to inhaled histamine at doses of 9.8, 39, 78, and 156 microg/ml was significantly inhibited by prior administration of 3 mg/kg of S-1452. PAF: the AHR to inhaled histamine at doses of 9.8, 39, and 78 microg/ml was significantly inhibited by prior administration of 1 mg/kg of Y-24180. CONCLUSIONS: S-1452 (3 mg/kg) and Y-24180 (1 mg/kg) significantly inhibited AHR to histamine, while ONO-108 (30 mg/kg) and indomethacin (5 mg/kg) did not. The results suggest that TXA(2) and PAF are involved in AHR in OA-sensitized guinea pigs.     

Increased airway responsiveness to acetaldehyde in asthmatic subjects with alcohol-induced bronchoconstriction.

Bronchial responsiveness to acetaldehyde, a main factor in alcohol-induced bronchoconstriction, and methacholine were compared between 10 subjects with alcohol-induced bronchoconstriction and 16 asthmatic subjects without alcohol sensitivity. In the alcohol-sensitive group, the geometric mean (geometric SEM (GSEM)) of the provocative concentration of methacholine (PC20,meth) and acetaldehyde (PC20,acet) causing a 20% fall in forced expiratory volume in one second were 0.947 mg x mL(-1) (GSEM 0.139) and 21.0 mg x mL(-1) (GSEM 0.112), respectively, which were not significantly different from those in the nonalcohol-sensitive group, which were 0.634 mg x mL(-1) (GSEM 0.115) and 31.7 mg x mL(-1) (GSEM 0.077), respectively. The ratio of airway responsiveness to acetaldehyde relative to methacholine (log PC20,acet/PC20,meth) was 1.345+/-0.093 (mean+/-SEM) in the alcohol-sensitive group, which was significantly different from the value of 1.699+/-0.059 in the nonalcohol-sensitive group (p=0.0025). A significant correlation was observed between PC20,meth and PC20,acet in both the alcohol-sensitive group (r=-0.742, p=0.0115) and nonsensitive group (r=0.882, p<0.0001). In conclusion, the airways of asthmatic subjects with alcohol-induced bronchoconstriction have a selective hyperresponsiveness to acetaldehyde.     

Effect of ozone exposure on airway responses to inhaled allergen in asthmatic subjects

BACKGROUND: Controlled human exposure studies have produced conflicting results regarding the effect of ozone on the early bronchoconstrictor response to inhaled allergen in specifically sensitized asthmatic subjects. Spirometric parameters do not necessarily reflect the airway inflammatory effects of inhaled ozone or allergen. OBJECTIVE: This study was designed to investigate whether exposure to ozone enhances the late airway inflammatory response, as well as the early bronchoconstrictor response, to inhaled house dust mite allergen in sensitized asthmatic subjects. DESIGN: Randomized, counter-balanced, cross-over study. SETTING: Human exposure laboratory. METHODS: Fourteen subjects were exposed to 0.2 ppm O(3) or filtered air, on separate days, for 1 h during exercise. After each exposure, the subjects were challenged with doubling doses of Dermatophagoides farinae (DF) allergen (provocative concentration of DF causing a 15% decrease in FEV(1) [PC(15)]). At 6 h after allergen challenge, bronchoscopy with BAL, proximal airway lavage (PAL), and endobronchial biopsy were performed. The second exposure/allergen challenge/bronchoscopy sequence was performed at least 4 weeks after the first sequence. RESULTS: No significant difference in cellular or biochemical markers of the late inflammatory response after allergen was found between the ozone and air exposures (although a trend toward increased neutrophils was noted after ozone exposure in the PAL fluid, p = 0.06). For the group as a whole, no significant difference in PC(15) was demonstrated after ozone exposure compared to air exposure. However, subjects with the greatest ozone-induced decrements in FEV(1) tended to have lower PC(15) values after ozone exposure. CONCLUSION: Exposure to a relatively low-level concentration of ozone does not enhance the late inflammatory or early bronchoconstrictor response to inhaled antigen in most allergic asthmatic subjects. Our results do suggest, however, that a subgroup of asthmatics may acquire increased sensitivity to aeroallergens after exposure to ozone.     

Influence of the menstrual cycle on airway function in asthmatic and normal subjects

Investigations of premenstrual asthma (PMA) have been based on studies of asthmatics already aware of a deterioration of asthma premenstrually. Little is known, therefore, about relationships between the menstrual cycle and airway function in asthmatics who do not complain of PMA or in normal subjects. We investigated airway function in both of these groups for three or four consecutive menstrual cycles. Daily records of asthma symptoms and peak expiratory flow rates were maintained by 11 asthmatics and 29 normal control subjects. Standard spirometry and serum estradiol and progesterone levels were measured during the follicular, midluteal, and late luteal phases of the menstrual cycle. Airway reactivity to methacholine was tested during the follicular and luteal phases. The normal group showed no significant changes in symptoms, peak flow rates, spirometric parameters, or airway reactivity. Although the asthmatic group also demonstrated no significant changes in spirometry and airway reactivity, asthma symptoms (shortness-of-breath, cough, wheeze, and chest tightness) deteriorated significantly (p less than 0.001) from the follicular to the luteal phase, as did the morning peak flows of the asthmatics (p = 0.045). Airway function and reactivity were not related to hormone levels in either group. This study indicates that asthmatics not previously aware of PMA will record a premenstrual worsening of asthma symptoms and peak expiratory flow rates. These changes are not related to a deterioration in spirometry and airway reactivity or to the absolute levels of circulating progesterone and estradiol.     

Bronchoalveolar lavage and morphology of the airways after cessation of exposure in asthmatic subjects sensitized to toluene diisocyanate

To evaluate the morphologic basis of the different outcomes of toluene diisocyanate (TDI) asthma after quitting occupational exposure, we examined ten patients with TDI asthma who showed, at diagnosis, a positive TDI challenge test and nonspecific bronchial hyperresponsiveness (NSBH) to methacholine. After diagnosis, all patients ceased work and a 4- to 40-month follow-up was obtained with three to eight determinations of the cumulative dose producing a 15 percent fall in FEV1 (PD15FEV1) methacholine in each patient. Bronchoalveolar lavage (BAL) and biopsy of bronchial muscosa were performed 3 to 39 months after cessation of work, in the absence of acute exacerbations of the disease. Total cell count in BAL fluid was moderately increased in four of ten patients, eosinophils were increased in five of ten patients, and neutrophils were increased in eight of ten patients. Mucosal biopsy specimens of main or lobar bronchi were available in eight of ten patients; epithelial damage and thickening of basement membrane was observed in almost all patients, as well as a mild-to-moderate inflammatory reaction in the submucosa, mainly represented by lymphocytes, eosinophils, and neutrophils. No relationship was observed between the cellularity of BAL and the degree of NSBH at the time of BAL; mean values of total cells and differential count were not different between patients with presence or absence of the different histologic findings. Mucosal biopsy and BAL were performed also in four subjects exposed to dusts without respiratory symptoms or NSBH; similar findings were obtained except for the absence of eosinophils in BAL and a lesser degree of basement membrane thickening and inflammatory reaction in the submucosa. The study of the changes in NSBH after quitting exposure showed that five of ten patients had a significant improvement in NSBH to methacholine, as evaluated by a positive significant linear regression between months of work cessation and PD15FEV1 methacholine; only one of these five patients had an increased number of eosinophils in BAL fluid. By contrast, four of the five patients with persistent NSBH after quitting exposure had an increased number of eosinophils in BAL. We suggest that persistent NSBH in TDI asthma after cessation of work may be related to an inflammatory reaction in which eosinophil infiltration seems to be a major determinant.     

Prednisone blunts airway neutrophilic inflammatory response due to ozone exposure in asthmatic subjects

BACKGROUND: The effect of corticosteroids on the ozone (O3)-induced airway inflammation is still debated. OBJECTIVE: The aim of the study was to confirm the effect of a short-term treatment with oral glucocorticosteroids on O3-induced airway inflammation, detected by induced sputum analysis, and on functional response in glucocorticosteroid-naive subjects. METHODS: A randomized, placebo-controlled study using oral prednisone (25 mg o.d. for 4 days) was carried out. Nine mild persistent asthmatics were exposed for 2 h, on separatedays, to 0.27 ppm O3 and to air in random order, after 4 days of treatment with prednisone (25 mg o.d.) and after 4 days of placebo.Before and after exposure, pulmonary function test was measured; 6 h afterexposure, sputum induction was done. RESULTS: Oral glucorticosteroids did not prevent pulmonary function decrement due to O3. After placebo, the percentage of neutrophils in induced sputum was significantly higher after O3 than after air [52.1 (15.7-77.3) vs. 17.8 (1.7-58.4), p=0.02, O3 vs. air]. This difference was lost after 4 days of treatment with prednisone [35.2% (10-96.2) vs. 30.9% (6.1-75.6), n.s., O3 vs. air]. Neutrophil elastase in sputum supernatant increased after O3 exposure in the sample obtained after placebo, but not after prednisone treatment. CONCLUSIONS: This study confirms that glucocorticosteroids reduce inflammatory airway response, but do not prevent the airway functional impairment after O3 exposure.     

Inflammatory mediators and cellular infiltration of the lungs in a guinea pig model of the late asthmatic reaction

Alterations in cell numbers, vascular permeability, and concentrations of various inflammatory mediators in the lung were measured in a guinea pig model of the late asthmatic reaction. Animals sensitized by inhalation of ovalbumin were challenged with an aerosol of ovalbumin or saline, and bronchoalveolar lavage fluid (BALF) and peripheral blood were collected after periods ranging from 5 min to 72 h. Increased vascular leakage within the lungs was indicated by elevated BALF/plasma albumin ratios at all time points, and was maximal 6 h after challenge. There were increased numbers of eosinophils in BALF by 6 h after challenge and they remained elevated at least until 72 h. A corresponding increase in the proportion of blood leukocytes represented by eosinophils was observed at 6 and 17 h, which suggests that these cells may be drawn to the lung following their release into the circulation, but by 72 h the proportion in blood had returned to normal. A transitory neutrophilia was evident in BALF and blood 6 h after allergen exposure, but there were no allergen-induced changes in BALF numbers of macrophages, lymphocytes, epithelial cells, or mast cells (as assessed by concentrations of cell-associated histamine). beta-Glucuronidase activity was significantly increased in BALF of guinea pigs at 2 h and 17 h following challenge. The degree to which eicosanoids can be recovered in BALF was investigated by instilling a range of tritiated compounds into the lungs of normal guinea pigs at the time of lavage. Ratio high-performance liquid chromatography revealed that there had been little metabolism of the eicosanoids recovered in BALF. However, there was evidence for a rapid removal of these mediators from the lung, a process which will militate against their accurate quantitation in BALF. Histamine, prostaglandin D2, and thromboxane B2 were detected in BALF but did not differ between treatment groups, and levels showed no simple relationship with the other inflammatory changes measured.     

Inflammatory mediators and cellular infiltration of the lungs in a guinea pig model of the late asthmatic reaction

Alterations in cell numbers, vascular permeability, and concentrations of various inflammatory mediators in the lung were measured in a guinea pig model of the late asthmatic reaction. Animals sensitized by inhalation of ovalbumin were challenged with an aerosol of ovalbumin or saline, and bronchoalveolar lavage fluid (BALF) and peripheral blood were collected after periods ranging from 5 min to 72 h. Increased vascular leakage within the lungs was indicated by elevated BALF/plasma albumin ratios at all time points, and was maximal 6 h after challenge. There were increased numbers of eosinophils in BALF by 6 h after challenge and they remained elevated at least until 72 h. A corresponding increase in the proportion of blood leukocytes represented by eosinophils was observed at 6 and 17 h, which suggests that these cells may be drawn to the lung following their release into the circulation, but by 72 h the proportion in blood had returned to normal. A transitory neutrophilia was evident in BALF and blood 6 h after allergen exposure, but there were no allergen-induced changes in BALF numbers of macrophages, lymphocytes, epithelial cells, or mast cells (as assessed by concentrations of cell-associated histamine).β-Glucuronidase activity was significantly increased in BALF of guinea pigs at 2 h and 17 h following challenge. The degree to which eicosanoids can be recovered in BALF was investigated by instilling a range of tritiated compounds into the lungs of normal guinea pigs at the time of lavage. Ratio high-performance liquid chromatography revealed that there had been little metabolism of the eicosanoids recovered in BALF. However, there was evidence for a rapid removal of these mediators from the lung, a process which will militate against their accurate quantitation in BALF. Histamine, prostaglandin D₂, and thromboxane B₂ were detected in BALF but did not differ between treatment groups, and levels showed no simple relationship with the other inflammatory changes measured.     

Acute exposure to sawdust does not alter airway calibre and responsiveness to histamine in asthmatic subjects

We investigated the effects of particles of sawdust delivered through a special device at known concentrations (close to the threshold limit value-short term exposure limit (TLV-STEL) of 10 mg.m-3) on FEV1 and PC20 in 12 asthmatic subjects free of clinical sensitization to this product. Subjects were studied over two days (day 1: exposure to sawdust; day 2: sham exposure) in random order with a maximum interval of 1 week. On each day, after the assessment of spirometry and PC20, subjects underwent exposure to sawdust or sham exposure. Sawdust was inhaled for a total of 30 min at average concentrations varying from 8.0 to 19.3 mg.m-3 (mean = 11.5 mg.m-3). Twenty-five to 39.7% (mean = 34.6%) of inhaled particles had a diameter less than 10 mu (diameter allowing deposition in the trachea and lower respiratory tract). At the end of each period of exposure, FEV1 was assessed. After recovery, the second PC20 was obtained. Serial measurements of FEV1 were carried out every hour for up to 6 h after the end of exposure. At that time, PC20 was reassessed. Only one subject showed an acute bronchoconstriction immediately after exposure to sawdust (maximum fall of 14% in FEV1) with complete recovery 10 min later. Overall, inhalation of sawdust did not modify PC20 by comparing the mean result of the first test with the second and the third assessments. Also, the mean changes in PC20 at each interval after exposure to sawdust were not significantly different from the variations in PC20 on the sham day.(ABSTRACT TRUNCATED AT 250 WORDS)     

Upper respiratory tract infections and airway reactivity in normal and asthmatic subjects

To assess the effect of an upper respiratory tract infection (URTI) on airway reactivity, histamine inhalation tests (HITs) were performed prospectively in 44 nonsmoking asthmatic (14) and nonasthmatic (30) volunteers. Fifteen of the subjects developed an URTI during the following 4 months. Pulmonary function-forced expiratory volume in one second (FEV1), maximal midexpiratory flow rates (MMEFR) and maximal flow at 50% vital capacity (V50), and HITs, were studied at onset and 2, 3, and 4 wk after infection. There were no significant changes in pulmonary function during the total study period. For the 15 subjects, the mean provocative concentration of histamine causing a 20% fall in FEV1, (PC20H) was 8.73 mg/ml prior to onset of URTI, and at 1, 2, 3, and 4 wk after URTI was 7.97, 8.68, 8.13, and 8.61 mg/ml. These were not significantly different for the group as a whole, nor for the subgroups of asthmatics and nonasthmatics. Small changes in PC20H outside the normal range of variability occurred in 5 of 15 subjects. These were short-lived and no predictive factor for change in PC20H was identified in this group. Thus, URTI was not associated with significant changes in PC20H in this group of asthmatic and nonasthmatic subjects.     

Effects of inhaled lidocaine on airway function in asthmatic subjects.

We measured the effect of inhaled lidocaine on pulmonary function in 8 asthmatic subjects. Plethysmographic specific airways conductance (SGaw) and the 1-sec forced expired volume (FEV1) were measured before and after the inhalation of 2cm3 of lidocaine (4%). Responses were also measured after patients were pretreated with either aerosolized isoproterenol, aerosolized atropine, or intramuscular atropine. In response to lidocaine alone, we observed a 23.4 +/- (SE) 4.8% fall in FEV1 and a 64.1 +/-(SE)3.8% fall in SGaw (p is less than 0.001). These effects were reversed with aerosolized atropine or isoproterenol. After pretreatment with aerosolized atropine or isoproterenol, the bronchoconstrictor effect of lidocaine were either prevented or markedly reduced. The protective effects of intramuscular atropine varied in different subjects, but in general, aerosolized bronchodilators afforded better protection against the bronchoconstrictor effect of lidocaine. Although lidocaine is theoretically capable of blocking neurogenic reflexes in the lung, our studies indicate that this topical anesthetic agent produces untoward reflex-mediated bronchoconstriction in patients with asthma and hyperirritable airways.