Biomedical subjects

E Crimi

Publications and source records attributed to E Crimi.

At least 55 records · Page 3Linked to original sources

PubMed1994

Bronchial provocation test with allergen: comparison between two different techniques.

Allergen bronchial provocation tests (BPTs) are often used for assessment of treatment efficacy. Usually, the allergen dose provoking a 20% fall of forced expiratory volume in one second (FEV1) (PD20) is determined on a prestudy day, and this single dose is administered for comparisons on study days. The inhalation of allergen may cause both an isolated early asthmatic response (EAR) or, more frequently, an EAR followed by a late asthmatic response (LAR). Whether the method used to elicit EAR, i.e. the inhalation of cumulative doses up to PD20 or the inhalation of a single predetermined PD20, give comparable results has not been established. We have, therefore, compared the results obtained using the two methods. Twelve patients underwent a first BPT with the increasing doses method and a second BPT with a single dose method. EAR, LAR, and allergen-induced increase of methacholine (MCh) sensitivity were compared. Both methods gave similar EAR's and LAR's although EAR tended to be more severe with the increasing dose method than with the single dose method. The ratio of postallergen/preallergen MCh sensitivity was poorly reproducible.

Adult↗

PubMed1993

Effect of multiple doses of nedocromil sodium given after allergen inhalation in asthma.

AIM: Twelve subjects with asthma took part in a placebo-controlled crossover study designed to investigate whether nedocromil sodium given after the occurrence of the early-phase asthmatic reaction to allergen has an effect on the late-phase response and the associated increase in airway responsiveness. METHODS: The treatments were administered four times at 4-hour intervals at a dose of 4 mg, with the first dose given 1 hour after the last allergen challenge. Changes in airway caliber were monitored for 15 hours after allergen exposure by measuring forced expiratory volume in 1 second hourly. Airway responsiveness to methacholine was determined 24 hours before and 24 hours after allergen challenge. RESULTS: Nedocromil sodium failed to reduce significantly the maximum late fall in forced expiratory volume in 1 second as compared with placebo but delayed its occurrence by 1.5 hours (p = 0.05). Nonspecific airway responsiveness to methacholine was similarly increased after allergen challenge when patients received nedocromil sodium and placebo. No unusual events were reported during the study period by any patient. These results indicate that nedocromil sodium is not able to interrupt the ongoing cascade of inflammatory events leading to the late-phase reaction and the associated increase in airway responsiveness. CONCLUSION: In allergic asthma, nedocromil can be used only as a preventive treatment.

Adult↗

PubMed1993

Frequency of allergen-specific T lymphocytes in blood and bronchial response to allergen in asthma.

BACKGROUND: This study was designed to investigate whether the bronchial response to the sensitizing allergen in asthma is correlated with the frequency of allergen-specific T lymphocytes. METHODS: Twenty-three asthmatic patients sensitized to Dermatophagoides pteryonyssinus who had never received hyposensitizing therapy and 11 healthy control subjects were studied. Allergen-specific T lymphocytes were enumerated in peripheral blood with limiting dilution cultures. Bronchial challenge with methacholine was performed in all subjects; patients with asthma also underwent an allergen bronchial challenge. Correlations between allergen-specific T cell frequencies and nonspecific bronchial hyperresponsiveness to methacholine as independent variables and early and late bronchial responsiveness to allergen challenge as dependent variables were investigated by means of stepwise-multiple regression analysis. RESULTS: We found that the frequency of allergen-specific T lymphocytes was higher than in control subjects in both patients with asthma with (p < 0.001) and those without (p < 0.05) late-phase asthmatic response to allergen. Moreover, the provocative does of allergen necessary to produce an early 15% fall of forced expiratory volume in 1 second could be predicted in part (59%) by an equation that incorporates methacholine sensitivity and allergen-specific T cell frequency. CONCLUSIONS: We conclude that allergen-specific T lymphocytes, which have an established influence on immunoglobulin E production, play an additional role in the induction of the bronchospastic response to inhaled allergen.

Adolescent↗

PubMed1993

Is the allergen-inhalation challenge predictive of the severity of seasonal asthmatic exacerbations?

Fifteen asthmatic patients sensitized to Parietaria pollen were studied. Before the pollen season they underwent an allergen-inhalation challenge which was preceded and followed by a methacholine-inhalation challenge. Pollen count, symptom score, and drug consumption were monitored daily throughout the study. A severity score was obtained by adding symptom score and drug consumption. Patients underwent a third methacholine challenge during the pollen season, after they had been exposed to a high atmospheric concentration of pollen. The severity score during the first period of the pollen season was significantly correlated with both the early and the late asthmatic responses to the allergen observed before the season (r2 = 0.50; P < 0.005). Bronchial sensitivity to methacholine was significantly increased both after allergen challenge and after seasonal exposure, but these increases correlated neither with each other nor with the severity score. We conclude that bronchial responses to experimental exposure to allergens, but not the changes in nonspecific airway responsiveness, can, in part, predict the severity of asthma exacerbation during the pollen season.

Adolescent↗

PubMed1993

Effects of aerosol methacholine and histamine on airways and lung parenchyma in healthy humans.

To investigate whether histamine (His) and methacholine (MCh) have different effects on airways and lung parenchyma, 11 healthy subjects were given aerosol MCh until a response plateau was obtained and then two doses of His. At the plateau, forced expiratory volume in 1 s and forced expiratory flow at 40% of vital capacity from partial flow-volume curves were reduced by 19 +/- 3 (SE) and 80 +/- 4%, respectively. Aerosol His decreased forced expiratory volume in 1 s by an additional 12 +/- 1% but left partial forced expiratory flow unchanged. The bronchodilator effect of deep inhalation, as inferred from the ratio of forced expiratory flow from maximal to that from partial flow-volume curves, increased after MCh and plateaued but decreased after His. Quasi-static transpulmonary pressure-volume area determined in seven subjects was unchanged after MCh but was increased by 57 +/- 10% after His. We conclude that adding His after the response to MCh plateaued does not increase the maximal degree of bronchoconstriction but may increase parenchymal hysteresis, thus blunting the bronchodilator effect of deep inhalation. These results suggest that His and MCh have similar effects on airway smooth muscle but different effects on lung tissue properties.

Adolescent↗

PubMed1993

Nimesulide does not interfere with airway responsiveness in allergic asthma.

The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) in asthmatic patients is limited by the possibility that these drugs may aggravate asthma by increasing the production of leukotrienes. Nimesulide, an NSAID with a weak inhibitory activity on prostaglandin synthetase, has been hypothesised to be safer than other NSAIDs in asthma. We have recently demonstrated in asthmatics who were allergic to the house dust mite that nimesulide neither alters the bronchial response to allergen nor aggravates the allergen-induced increase in airway responsiveness.

Animals↗

PubMed1992

Relationship between quasi-static pulmonary hysteresis and maximal airway narrowing in humans.

Two groups of subjects were studied: one with (group 1: 5 healthy and 4 mildly asthmatic subjects) and another without (group 2:9 moderately and severely asthmatic subjects) a plateau of response to methacholine (MCh). We determined the effect of deep inhalation by comparing expiratory flows at 40% of forced vital capacity from maximal and partial flow-volume curves (MEF40M/P) and the quasi-static transpulmonary pressure-volume (Ptp-V) area. In group 1, MEF40M/P increased from 1.58 +/- 0.23 (SE) at baseline up to a maximum of 3.91 +/- 0.69 after MCh when forced expiratory volume in 1 s (FEV1) was decreased on plateau by 24 +/- 2%. The plateau of FEV1 was always paralleled by a plateau of MEF40M/P. In group 2, MEF40 M/P increased from 1.58 +/- 0.10 at baseline up to a maximum of 3.48 +/- 0.26 after MCh when FEV1 was decreased by 31 +/- 3% and then decreased to 2.42 +/- 0.24 when FEV1 was decreased by 46 +/- 2%. Ptp-V area was similar in the two groups at baseline yet was increased by 122 +/- 9% in group 2 and unchanged in group 1 at MCh end point. These findings suggest that the increased maximal response to MCh in asthmatic subjects is associated with an involvement of the lung periphery.

Adult↗

PubMed1992

Bronchial and bronchoalveolar lavage after allergen challenge in atopic patients.

Twenty patients with allergic rhinitis and/or asthma sensitised to Dermatophagoides pteronyssinus were studied. On two consecutive days they underwent methacholine challenge and allergen bronchial challenge. 72 h after allergen challenge, fibreoptic bronchoscopy with bronchial (BL) and bronchoalveolar (BAL) lavage was performed. Specific IgE antibodies were measured both in serum and in BL from 14 patients. Both BAL and BL cell differentials were similar in patients with isolated early response to allergen and in patients with dual response. Patients with dual response to allergen showed higher levels of antigen specific IgE antibodies in BL than patients with isolated early response, while IgE levels in serum were similar in the two groups.

Adolescent↗

PubMed1992

Increase in airway responsiveness and effect of deep inhalation on airway caliber in allergen-induced asthma. Relationship to the late-phase response.

The airway responsiveness to methacholine (MCh) and the effect of deep inhalation (DI) on airway caliber were determined in 18 asthmatic patients at baseline and 3 and 24 h after an allergen inhalation challenge. The dose of MCh causing a 20% fall of FEV1 (PD20) was used as an index of airway responsiveness; the ratio of forced expiratory flow at 40% of FVC from maximal and partial flow/volume curves (MEF40M/P) was used to assess the effect of DI on airway caliber. Thirteen patients showed a dual asthmatic response (DAR) to allergen, 5 patients an isolated early-phase asthmatic response (EAR). In the DAR patients, 3 h after allergen challenge, when the early-phase response had resolved and the late-phase response had yet to develop, MChPD20 (geometric mean) was reduced from 202 to 71 micrograms (P less than 0.001) whereas MEF40M/P at the MCh end point was unchanged (p greater than 0.4). Twenty-four hours after allergen challenge, when late-phase response had developed, MChPD20 was further reduced to 51 micrograms (p less than 0.02), and this reduction was accompanied by a decrease of MEF40M/P at the MCh end point (p less than 0.01). In the EAR patients, neither MChPD20 nor MEF40M/P was significantly changed at any time during the study. We conclude that most of the increase in airway responsiveness that follows acute exposure to allergen precedes the late-phase response and is not determined by the same mechanisms that impair the ability of the lung to dilate airways with a DI.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1992

Airway inflammation and occurrence of delayed bronchoconstriction in exercise-induced asthma.

We studied nine asthmatic patients with a history of exercise-induced asthma (EIA) in order to investigate whether inflammatory changes in the airways occur after exercise and are eventually associated with the development of a late-phase asthmatic response. On two separate study days, bronchoalveolar lavage (BAL), bronchial lavage (BL), and bronchial biopsy (BB) were performed 3 h after an exercise or a methacholine (MCh) challenge. On two other separate occasions, FEV1 was monitored for 12 h after identical exercise and MCh challenges not followed by BAL, BL, and BB. We found a greater percentage of eosinophils in BAL after exercise versus MCh challenge (p < 0.05). In five patients, BAL eosinophils after exercise were > or = 2% of total inflammatory and immunoeffector cells. In three of these patients an FEV1 fall > 20% of control was recorded 5 to 12 h after exercise. However, two of these patients had 2% or more eosinophils in BAL and similar late falls of FEV1 after MCh challenge. The percentage of degranulating mast cells in BB was higher (p < 0.05) after EIA than after MCh, but no significant differences were found in BL histamine and leukotrienes. We conclude that (1) exercise may enhance mast cell degranulation and eosinophilic inflammation of the airways, and (2) a delayed bronchoconstriction after exercise is not specific to EIA but is more likely the result of fluctuations in lung function associated with airway inflammation.

Adult↗

PubMed1991

Local immunotherapy with Dermatophagoides extract in asthma.

Local immunotherapy (LIT) with Dermatophagoides extract or placebo were administered to two groups of 11 patients with allergic asthma in a double-blind fashion. All patients received cromolyn sodium (20 mg four times a day) during treatments. Bronchial provocation tests with allergen and methacholine were performed before, 1 week, and 4 weeks after the end of treatments. Symptom score, drug consumption, and peak expiratory flow were monitored daily from 2 weeks before to 4 weeks after treatments. Compared to baseline, early bronchial sensitivity to allergen was significantly reduced both 1 week (p less than 0.0005) and 4 weeks (p less than 0.01) after LIT but not after placebo administration. Late bronchial reaction to allergen occurred similarly after placebo administration and LIT. However, in the group with LIT, the severity of late reaction was unchanged after treatment in spite of the significantly larger doses of allergen administered to provoke the early asthmatic reaction. Neither symptom score, nor drug consumption, nor peak expiratory flow were significantly different in the two groups before and during the treatment period even though both symptom score and drug consumption tended to be reduced after LIT. We conclude that LIT may be an effective and safe alternative to traditional immunotherapy.

Adolescent↗

PubMed1991

Bronchial responsiveness is not increased by bronchoalveolar and bronchial lavage performed after allergen challenge.

Nonspecific bronchial responsiveness was studied in 23 allergic patients with a history of rhinitis and/or bronchial asthma who underwent fiberoptic bronchoscopy with bronchoalveolar and bronchial lavage (BAL-BL) 4h (Group A) or 24 h (Group B) after an allergen inhalation challenge. In all patients, the dose of methacholine causing an FEV1 fall of 15% (PD15) was determined at baseline, 24 h before allergen challenge. Methacholine bronchial challenge was repeated 1 h before BAL-BL in patients of both groups and again 12 to 14 h after BAL-BL in Group A and 24 h after BAL-BL in Group B. In patients of Group A, the values of methacholine PD15 after BAL-BL were not significantly different from those determined before BAL-BL. This was also the case in patients in whom bronchial responsiveness was increased after allergen challenge. In patients of Group B, methacholine PD15 was significantly decreased after allergen challenge, and this decrease was correlated with the occurrence and the severity of the late asthmatic reaction. Even in patients who showed dual asthmatic reactions and an increased responsiveness after allergen challenge, methacholine PD15 was not further decreased after BAL-BL. These data support the safety of a procedure combining bronchial allergen challenge with BAL-BL, which can be used for studies on the pathophysiology of bronchial asthma.

Adolescent↗

PubMed1991

Late-phase asthmatic reaction to inhaled allergen is associated with early recruitment of eosinophils in the airways.

To determine whether a link exists between the recruitment of inflammatory cells in the airways and the development of the late-phase asthmatic reaction, we studied with bronchoalveolar lavage 54 asthmatic patients either at baseline (10 patients) or 4 h (11 patients), 24 h (13 patients), and 72 h (20 patients) after allergen inhalation challenge. Among the patients studied 4 h after allergen challenge, five were known to have a late-phase asthmatic response and showed a significant increase in the number and percentage of eosinophils in bronchoalveolar lavage compared with either patients without late-phase response (p less than 0.05) or unchallenged patients (p less than 0.01). Both the number and the percentage of eosinophils in bronchoalveolar lavage were also increased (p less than 0.05) in patients without a late-phase asthmatic reaction studied 24 h but not in those studied 4 h after allergen challenge. The numbers and the percentages of macrophages, neutrophils, or lymphocytes did not differ significantly among the different groups of patients. Of the patients studied 4 and 24 h after allergen challenge, only those with a late-phase asthmatic response showed an increased airway responsiveness to methacholine 1 h before bronchoalveolar lavage. We conclude that the development of the late-phase asthmatic response to allergen inhalation challenge and the allergen-induced increase in airway responsiveness are associated with an early recruitment of eosinophils in the airways.

Adolescent↗

PubMed1991

Time course and calcium dependence of sustained bronchoconstriction induced by deep inhalation in asthma.

We studied six asthmatic patients who showed a progressive decrease in FEV1 when successive forced expiratory maneuvers were performed at 1-min intervals. We determined the time course of changes in specific airway conductance following a single deep inhalation (DI) and the ratio of maximum expiratory flow at 40% of FVC from maximal and partial flow-volume curves (MEF40M/P) during a series of forced expiratory maneuvers. Specific airway conductance measured 3 s after DI was increased by 11 +/- 6 (SE)%, which was not significantly different from an increase of 23 +/- 8% observed in six healthy control subjects. Later (i.e., 10 to 40 s after DI) specific airway conductance was significantly less than the pre-DI value in asthmatic but not in healthy subjects. Mean FEV1 decreased significantly by 28% from the first to the eighth forced expiratory maneuver performed during a period of 15 min, whereas MEF40M/P was not significantly changed and remained always significantly greater than 1. The voltage-dependent calcium channel antagonist nifedipine significantly prevented the reduction of FEV1 without affecting MEF40M/P. We conclude that, in some asthmatic individuals, DI may induce a transient bronchodilatation followed by a calcium-dependent sustained bronchoconstriction. We suggest that the initial bronchodilatation is due to the mechanical interdependence between airways and lung parenchyma, whereas the sustained bronchoconstriction is due to contraction of the airway smooth muscle.

Adult↗

PubMed1991

Increased numbers of mast cells in bronchial mucosa after the late-phase asthmatic response to allergen.

We examined the characteristics of allergen-induced inflammation of the bronchial mucosa in asthmatic patients. Studies were carried out 4 h (eight patients) and 24 h (nine patients) after allergen inhalation challenge; 10 patients were not challenged and served as control subjects. We found that in the control group the ratio of degranulating to granulated mast cells was higher in patients with than in patients without late-phase response. In patients studied 4 h after allergen challenge the total number of mast cells was not significantly different from that in control subjects; the ratio of degranulating to granulated mast cells was increased similarly in patients with and without late-phase response. Among patients studied 24 h after allergen challenge, those who had developed the late-phase response had an increased (p less than 0.05) number of mast cells as compared with patients who had not developed the late-phase response, the number of mast cells was significantly correlated with the severity of the late-phase response (r = 0.80; p less than 0.001). The numbers of eosinophils and mononuclear cells and the morphologic abnormalities of bronchial structure (altered ratio of cylindrical to goblet cells, thickening of the basement membrane, and edema and angiectasis of lamina propria) were similar in the different groups of patients. We conclude that the inflammatory events leading to the development of the late-phase asthmatic response to allergen represent a stimulus for an increase in the number of mast cells in the bronchial mucosa.

Adult↗

PubMed1991

Antiinflammatory-antioxidant treatment with a methane sulfonanilide in allergen-induced asthma.

Two groups of six asthmatic patients with biphasic bronchospastic response to inhaled Dermatophagoides pteronyssinus allergen extract were studied in a double-blind fashion. Early and late asthmatic reactions to allergen inhalation challenge were determined before and at the end of a 2-week treatment period with nimesulide (100 mg bid orally), a sulfonanilide with antioxidant properties, or placebo. Bronchial responsiveness to methacholine was evaluated 24 hours before and after allergen inhalation challenges. The dose of allergen causing EAR (15% decrease in FEV1) and the severity of LAR (maximum FEV1 fall) were similar before and at the end of the treatment period in both groups. In patients treated with nimesulide, bronchial responsiveness to methacholine was significantly increased after allergen inhalation challenge both before and at the end of the treatment period. These results do not support the hypothesis that the production of oxygen-free radicals plays a significant role in the development of bronchial hyperresponsiveness and late phase reaction to allergen in asthma.

Adolescent↗

PubMed1990

Effect of seasonal exposure to pollen on specific bronchial sensitivity in allergic patients.

Bronchial provocation tests with aerosol of birch extract were performed before and after pollen season in 11 sensitized subjects. Changes of metacholine bronchial responsiveness and serum-specific IgE level were also assessed. In five patients who did not take steroids to control their symptoms, both early and late asthmatic responses to inhaled allergen were enhanced after season, whereas IgE serum level, but not methacholine sensitivity, was significantly increased. In six patients who needed steroids, neither responses to allergen nor IgE serum level and methacholine sensitivity were significantly changed after season. For the whole group, the increase in immediate bronchial sensitivity to allergen was positively correlated with the increase in specific IgE antibodies. We conclude that seasonal exposure to pollen has, in sensitized patients, a priming effect on bronchial mucosa that may be blunted by steroid treatment. The increased production of specific IgE antibodies appears to be an important mechanism for this priming effect.

Antibodies↗

PubMed1990

Late asthmatic reaction to perennial and seasonal allergens.

Twelve patients with asthma sensitized to Dermatophagoides pteronyssinus and Parietaria judaica were studied. Patients were challenged before (winter), during (summer), and after (autumn) Parietaria-pollen season. Early asthmatic reaction was positive for both allergens, and the provocative dose causing a 15% decrease of FEV1 was similar in all seasons. The provocative dose of methacholine causing a 15% decrease of FEV1 and specific IgEs for both allergens were also not significantly different throughout the time of study. Late asthmatic reaction (LAR) to Dermatophagoides occurred in eight of 12 patients in winter, in six of nine in summer, and in five of six patients in autumn. The severity of LAR, expressed as the maximum fall of FEV1 3 to 8 hours after challenge, was not significantly different between seasons. LAR to Parietaria occurred in only one of 12 patients in winter, in six of 11 in summer, and in one of six patients in autumn. In summer, LAR to Parietaria was significantly more severe than in winter. In both winter and autumn, but not in summer, LAR to Dermatophagoides was significantly more severe than to Parietaria. We conclude that LAR is allergen specific, and natural exposure has a priming effect on LAR.

Adolescent↗