Eosinophil apoptosis in induced sputum from patients with seasonal allergic rhinitis and with asymptomatic and symptomatic asthma.

BACKGROUND: Eosinophilic inflammation is known to play an important role in the pathogenesis of allergic diseases. Apoptosis, a form of programmed cell death, is characterized by morphologic cell changes and leads to recognition and ingestion by macrophages. Apoptosis could be an important mechanism controlling the resolution of tissue eosinophilia. OBJECTIVE: This study was designed to investigate the presence of apoptotic eosinophils in induced sputum of patients with seasonal allergic rhinitis (SAR), when examined during natural pollen exposure and of patients with perennial asthma of different degrees of severity. METHODS: We recruited 11 patients with SAR to grass pollens, 26 patients with asymptomatic asthma (AA), and 18 patients with symptomatic asthma (SA). The severity of asthma was assessed by clinical scoring. Sputum was induced following a standard method and differential cell count was estimated. Eosinophils showing cell shrinkage and nuclear coalescence were classified as apoptotic. The number of apoptotic eosinophils was expressed as the percentage of total cells in sputum and as the proportion of apoptotic eosinophils relative to normal bilobed eosinophils ("apoptotic ratio"). RESULTS: We found the number of eosinophils in the SA group was significantly greater than that in the SAR and the AA groups (P < .001 and P < .0001 respectively). The number of apoptotic eosinophils in the AA group was significantly lower than that in the SAR group (P < .001) and in the SA group (P < .0001). The apoptotic ratio for eosinophils in the SAR group was significantly greater than in the AA group (P < .05) and in the SA group (P < .05). There was no difference in the apoptotic ratio between the AA and SA groups. CONCLUSIONS: This study confirms that apoptotic eosinophils are detectable in induced sputum of allergic patients. Further, the results of our study suggest that apoptosis could be an important mechanism in the control of acute eosinophilic inflammation in patients with SAR exposed to the sensitizing antigens. It appears that the apoptotic mechanism could be less effective in controlling tissue eosinophilia in asthmatic patients with chronic eosinophilic inflammation.

Eosinophils, mast cells, and basophils in induced sputum from patients with seasonal allergic rhinitis and perennial asthma: relationship to methacholine responsiveness.

OBJECTIVES: We attempted to determine whether inflammation is present in induced sputum of patients with seasonal allergic rhinitis (AR) as compared with those with perennial asthma (AS) and examined its relationship with bronchial responsiveness to methacholine. METHODS: Sputum was induced in 30 patients with seasonal rhinitis in response to grass pollens only and in 15 patients with stable, asymptomatic asthma. The AR group was divided according to methacholine PD20 value: the AR- group (n = 15) had a methacholine PD20 greater than 24 micromol; the AR+ group (n = 15) had a methacholine PD20 ranging between 2.2 and 19.6 micromol. In the AS group, methacholine PD20 ranged between 0.42 and 2.6 micromol. The percentage of eosinophils and metachromatic cells (alcian blue-positive) was assessed in sputum by light microscopy. Tryptase-positive cells and EG2+ cells were identified by immunocytochemistry with the mouse anti-human mast cell-tryptase monoclonal antibody and the monoclonal anti-eosinophil cationic protein antibody. RESULTS: We found that the number of eosinophils in the AS group was greater than that in the AR+ group (p < 0.05) and in the AR- group (p < 0.01). Moreover, the eosinophil count was lower in the AR- group compared with the AR+ group (p < 0.05). Similarly, the number of EG2+ cells was greater in the AS group than in the AR group (p < 0.02) and the AR- group (p < 0.05). Moreover, the EG2+ cell count was lower in the AR- group than in the AR+ group (p < 0.05). The number of mast cells and basophils in the AS group was greater than that in the AR group (p < 0.05 and p < 0.01, respectively). Mast cells in sputum were tryptase-positive. Basophils were present in sputum from 23% of patients with AR and 53% of patients with asthma. There was a significant correlation between methacholine PD20 and eosinophils (p < 0.005) and mast cells (p < 0.02) but not with basophils in those patients showing a measurable methacholine PD20 (AR+ and AS groups). CONCLUSIONS: Inflammatory cells are present not only in the airways of patients with asthma but also in airways of patients with seasonal AR, even outside natural exposure. Moreover, we provide evidence for the presence of basophils in sputum of patients with asthma even during clinical remission. The presence of bronchial responsiveness is associated with an increase in the number of eosinophils and metachromatic cells. Our findings are consistent with the hypothesis that eosinophils, as well as mast cells, contribute to bronchial responsiveness not only in AS but also in seasonal AR.

Effect of inhaled furosemide and cromolyn on bronchoconstriction induced by ultrasonically nebulized distilled water in asthmatic subjects.

BACKGROUND: Inhaled furosemide has been shown recently to produce a protective effect against bronchoconstriction induced by several indirect stimuli, including ultrasonically nebulized distilled water (UNDW). Since there is a close parallel between its experimental effects and those reported for cromolyn,/it has been suggested that they may share some common mechanisms of action. Their protective effect, however, has never been compared directly. In this study, therefore, we have investigated the ability of equal doses (30 mg) of inhaled furosemide and cromolyn to modulate bronchoconstriction induced by UNDW in a group of ten asthmatic patients. METHODS: Subjects with documented bronchial response to UNDW were enrolled in a randomized, double-blind, placebo-controlled study. Treatments were administered five minutes prior to increasing outputs of UNDW and the response was expressed as the provocative output causing a 20% fall in FEV1 (PO20, in mL/min) and as the output-response slope. RESULTS: Geometric mean PO20 increased from 1.53 to 4.05 mL/min (P < .0004) after furosemide. After inhaling the highest output of UNDW (5.2 mL/min), PO20 was not measurable in six of ten patients when pretreated with furosemide and in all patients when pretreated with cromolyn. This difference was statistically significant (P < .05). Geometric mean values of output-response slope significantly decreased from 13.6 to 2.97 after furosemide (P < .0001) and from 13.6 to 1.43 (P < .0002) after cromolyn. CONCLUSIONS: These results suggest that cromolyn has a slightly greater anti-reactive activity in UNDW-induced bronchoconstriction compared to furosemide.

[Validity, limitations and indications of intraoperative dosage of parathyroid hormone (I-PTH) in the surgical treatment of primary hyperparathyroidism]. / Validità, limiti ed indicazioni del dosaggio intraoperatorio del paratormone (I-PTH) nel trattamento chirurgico dell'iperparatiroidismo primario.

INTRODUCTION: Recently new methods have been experienced to achieve the best surgical results in complete removal of pathological parathyroid tissue; serum I-PTH (1-84) rapid dosage is the most interesting and reliable method. MATERIAL AND METHODS: In a group of 11 patients with IPP, diagnosed by high levels of I-PTH, total and ionized serum calcium, 7 were paucisymptomatic, 3 presented nephrolityasis, 1 acute pancreatitis and severe hypercalcemic crisis. No MEN were found. A systemic research of all parathyroid glands was always performed, then 10, 20, 30 and any 30 minutes after each parathyroidectomy serum I-PTH rapid dosage was made (rapid IRMA method) until the end of surgical treatment. RESULTS: Eight single adenomas parathyroid were diagnosed, 1 double adenoma and 2 hyperplasia. All patients had high levels of serum I-PTH during pathologic parathyroid removal. The decrement of I-PTH level to 40% 10 min after parathyroidectomy, and 50% after 20 minutes confirmed the efficacy of surgery. DISCUSSION: Intraoperative rapid dosage of I-PTH associated with anatomopathologic results leads to a successful diagnosis and therapy. Sometimes in multiglandular disease serum level of PTH decreases after first parathyroidectomy as in a single adenoma: this underlines the importance of systematic surgical research of all glands in any case. CONCLUSION: In our experience serum I-PTH rapid dosage in IPP would be applied by specialized surgical equipments only in selected patients, such as reoperation or those few cases of first surgical treatment when ectopy is suspected.

Bronchial responsiveness and airway inflammation in patients with nonallergic rhinitis with eosinophilia syndrome.

BACKGROUND: Nonallergic rhinitis with eosinophilia syndrome (NARES) is characterized by persistent nasal symptoms without allergy and by a marked eosinophil recruitment in the nasal cavities. OBJECTIVE: We studied whether patients with NARES had bronchial responsiveness to methacholine and airway inflammation and examined the relationship between these factors. METHODS: We selected a group of 39 patients referred to our allergy clinic for symptoms of perennial rhinitis. Atopic status was excluded by skin prick tests and RASTs. None of the patients had a history of respiratory symptoms. We preliminarily performed nasal lavage in all patients, and the diagnosis of NARES was made on the basis of the presence of at least 10% eosinophils in nasal lavage fluid. A methacholine challenge and sputum induction were also done on two different days. RESULTS: Eosinophils in nasal lavage fluid ranged between 10% and 86%. Serum IgE levels were within normal range. Total circulating eosinophils ranged between 40 and 890/mm3. Methacholine PD20 values were measurable in only 18 patients (range, 0.32 to 22.56 micromol; group 1). In the remaining 21 patients, methacholine PD20 values were greater than 24 micromol (group 2). We found that differential cell counts in nasal lavage fluid in group 1 were not different from those in group 2. Methacholine PD20 values were not significantly related to any cell count in the nasal lavage fluid. Induced sputum was accomplished only in 22 patients. Eosinophils in induced sputum ranged between 0% and 56.5%. Numbers of total cells, macrophages, lymphocytes, neutrophils, and epithelial cells in the two subgroups were not different. The number of metachromatic cells tended to be higher in group 1 compared with group 2 (0.31% vs 0.05%), but the difference was not significant. The eosinophil count in the induced sputum was significantly higher in group 1 compared with group 2 (16.8% vs 3.1%; p < 0.05). In the entire population, methacholine PD20 values were significantly correlated with the number of eosinophils in sputum (r = -0.63; p < 0.001). CONCLUSION: We showed that 46% of patients with NARES but without histories of respiratory symptoms had a measurable bronchial responsiveness. The presence of bronchial responsiveness was associated with an increased number of eosinophils in induced sputum but not with the inflammatory process in the nose.

Once daily intranasal fluticasone propionate (200 micrograms) reduces nasal symptoms and inflammation but also attenuates the increase in bronchial responsiveness during the pollen season in allergic rhinitis.

BACKGROUND: Fluticasone propionate aqueous nasal spray, a new topical corticosteroid, has been proved to be an effective treatment for seasonal allergic rhinitis. OBJECTIVES: We studied the effect of fluticasone propionate on nasal symptoms, circulating eosinophils, and nasal inflammation in patients with seasonal allergic rhinitis after high-load pollen exposure. Moreover, we examined its efficacy in preventing the increase in bronchial responsiveness to methacholine (PD20) during the pollen season. METHODS: We conducted a double-blind, placebo-controlled, parallel-group study in patients who had a history of allergic rhinitis in response to pollens of grass and Parietaria species and were living in northern Italy. After a run-in period of 2 weeks, 24 patients were treated with fluticasone propionate (200 micrograms, once daily), and 26 patients received matched placebo for 6 weeks, starting from the beginning of the pollen season. Assessment of efficacy was based on scores of daily nasal symptoms. Nasal lavage was performed at the end of the season, and differential cell count was expressed as percent of total cells. PD20 methacholine was measured at the beginning and end of the season and after the season had ended. RESULTS: Fluticasone propionate significantly reduced nasal obstruction, itching, and rhinorrhea. Eosinophils in blood (p < 0.01) and nasal lavage (p < 0.001) were also reduced. Moreover, fluticasone significantly attenuated the decrease in mean PD20 methacholine (from 1.95 to 0.89 mg) compared with placebo (from 1.38 to 0.37 mg: p < 0.01). After the season, no difference in PD20 methacholine was found between treatment groups. CONCLUSIONS: The results of this study indicate that fluticasone propionate is effective in decreasing nasal symptoms and eosinophil inflammation in patients with seasonal allergic rhinitis after high-load pollen exposure. Our results also demonstrate that treatment with fluticasone propionate partially prevents the increase in bronchial responsiveness provoked by the inhalation of seasonal pollens in allergic rhinitis.

Effect of acetazolamide on cough induced by low-chloride-ion solutions in normal subjects: comparison with furosemide.

BACKGROUND: The antitussive activity of inhaled furosemide has been attributed to its blocking effect on the Na(+)-2Cl(-)-K+ cotransporter. It is likely that the antitussive activity of inhaled diuretics is more complex because amiloride, a diuretic that has no effect on the Na(+)-2Cl(-)-K+ cotransporter, also shows a significant effect against cough induced by low-chloride-ion solutions. Apart from pharmacokinetics of inhaled diuretics, this activity could also depend on the inhibition of carbonic anhydrase. OBJECTIVES: We therefore studied the effect of inhaled acetazolamide, a selective inhibitor of carbonic anhydrase activity, on cough induced by the inhalation of different chloride ion solutions in a group of normal subjects. This was compared with the antitussive effect of furosemide. In addition, we attempted to determine whether the effect of acetazolamide is dose-dependent. METHODS: Cough challenge consisted of consecutive inhalations of four solutions having decreasing concentrations of chloride ions (150, 75, 37.5 and 0 mmol/L). Nine normal subjects underwent the cough challenge 5 minutes after the inhalation of saline placebo, acetazolamide (500 mg), and furosemide (30 mg) according to a randomized, double-blind study design. A group of six subjects were challenged according to the same procedure and study design, after the inhalation of saline placebo and of two doses of acetazolamide (250 mg and 500 mg). RESULTS: Inhaled acetazolamide significantly reduced cough response to 37.5 and 0 mmol/L chloride solutions compared with placebo (p less than 0.015 and p less than 0.015, respectively). Furosemide showed a similar protective effect (p less than 0.015 and p less than 0.025, respectively). Acetazolamide provided a significantly better protective effect than furosemide (p less than 0.025 and p less than 0.015, respectively). The antitussive activity of the two doses of acetazolamide was not statistically different. CONCLUSION: These results demonstrate that inhaled acetazolamide, a selective inhibitor of carbonic anhydrase, attenuates cough induced by low-chloride-ion solutions in normal subjects. At the applied doses, its antitussive activity is slightly greater than furosemide. This finding suggests that the inhibition of carbonic anhydrase activity is likely involved in modulating changes caused by absence of a chloride ion in the airway microenvironment of human beings.

Prevalence and repeatability of the cough response induced by inhalation of low chloride ion solutions in normal subjects.

Although the inhalation of low Cl- ion solutions has often been used to induce cough, the prevalence and repeatability of the challenge has never been studied in detail. We, therefore, examined cough response in a group of 59 volunteers (aged 15-57 yrs; 34 females and 25 males; 20 smokers) to ascertain prevalence and repeatability. Each subject performed, 2 weeks apart, two identical cough challenges by inhaling four isosmolar solutions with decreasing Cl- ion concentrations (150, 75, 37.5 and 0 mM). Each solution was delivered by a DeVilbiss 65 ultrasonic nebulizer (mean output: 1.9 mL.min-1) for 1 min, and the number of coughs was counted during the inhalation. Cough response was expressed as number of coughs.min-1. Significance of response to the cough challenge was assessed on the basis of mean number of coughs.min-1 and 95% upper confidence limit (CL) of response to the Cl- free solution in the whole population. Cough threshold for a significant response was greater than 8 coughs.min-1. Out of 59 subjects, only 20 exceeded the cough threshold (34%) after inhaling the Cl- free solution. A concentration-response effect was evident only when inhaling 37.5 and 0 mM Cl- ion solutions. A significant cough response was more likely among females (p = 0.03). Smoking did not significantly affect the prevalence of response. Coefficients of repeatability of cough response to 37.5 and 0 mM Cl- solutions in 20 responders were equal to 10.1 and 12.6, respectively. We conclude that a significant cough response to low Cl- ion solutions develops in approximately 1 out of 3 of challenged volunteers and that repeatability is not satisfactory. We suggest that cough threshold and repeatability should be preliminarily assessed, especially when the challenge is used to study the antitussive activity of drugs.

Effect of intranasal azelastine and beclomethasone dipropionate on nasal symptoms, nasal cytology, and bronchial responsiveness to methacholine in allergic rhinitis in response to grass pollens.

BACKGROUND: We compared the effect of nasal azelastine (0.56 mg/day), nasal beclomethasone dipropionate (BDP, 200 micrograms/day) and matched placebo on seasonal symptoms, nasal cytology, and the increase in bronchial responsiveness occurring during pollen season in a group of subjects with history of allergic rhinitis to grass pollens only. METHODS: The study was completed by nine subjects in the azelastine group, 13 subjects in the BDP group, and 13 subjects in the placebo group. Treatments were randomly administered for 6 weeks. Each subject recorded daily nasal, eye and chest symptoms and additional treatment requirement for the entire pollen season. Each subject performed nasal lavage 4 weeks into the pollen season. Bronchial responsiveness to methacholine was measured before and 4 weeks into the pollen season. Response was expressed as provocative dose causing a 20% fall in forced expiratory volume in 1 second in micromoles. RESULTS: Azelastine-treated subjects had significantly fewer nasal symptoms during week 4 (p < 0.05), and BDP-treated subjects had fewer nasal symptoms during week 4 (p < 0.05) and week 5 (p < 0.05) compared with subjects given placebo. Both treatments significantly reduced the need for additional medications. BDP, but not azelastine, treatment significantly reduced the percent of eosinophils recovered in nasal lavage (p < 0.05). Neither azelastine nor BDP protected against the increase in bronchial responsiveness to methacholine occurring during the pollen season. CONCLUSION: We demonstrated that both azelastine and BDP are effective treatments for nasal symptoms of seasonal allergic rhinitis after 4 weeks of therapy. However, we were not able to demonstrate an antiinflammatory activity of nasally administered azelastine. Nasal therapy with azelastine and BDP did not block the increase in bronchial responsiveness to methacholine caused by seasonal allergen exposure.

Lung function and diffusing capacity for carbon monoxide in patients with juvenile chronic arthritis: effect of disease activity and low dose methotrexate therapy.

OBJECTIVE: We measured lung function, in terms of lung volumes, forced expiratory flow-volume curves and diffusing capacity of carbon monoxide (DLCO), in a group of 61 patients with juvenile chronic arthritis (42 female; age range 5 to 33 years) to ascertain whether disease activity and treatment with low dose methotrexate (MTX) influenced these parameters. The whole population was divided into subgroups based on onset type (systemic, n = 27; pauciarticular, n = 12; polyarticular, n = 22), disease activity (active, n = 42; inactive, n = 19), and MTX treatment (treated, n = 27; not treated, n = 34). RESULTS: We found that maximal-mid expiratory flow (MMEF) was significantly reduced in patients with active disease (p < 0.025). The mean DLCO value, expressed as a percentage of the predicted value, and DLCO corrected for the hemoglobin value were lower than expected (67% and 80%, respectively). Multiple regression analysis showed that the forced vital capacity (FVC), forced expiratory flow in one second (FEV1) and DLCO were all correlated to the clinical subtype of the disease (p < 0.05, p < 0.02, p < 0.02, respectively), and MMEF was related to disease activity (p < 0.025). There was no evidence of any effect of MTX treatment on the pulmonary parameters. CONCLUSION: This study confirms that JCA is characterized by an impairment of lung function, mainly involving the small airways, and by interstitial damage. These changes are related to the clinical subtypes of the disease and to disease activity.

Reproducibility of allergen-induced asthma and associated increase in bronchial responsiveness to methacholine in asthmatic children.

We studied the reproducibility of early (EAR) and late (LAR) asthmatic response to allergen challenge in 13 asthmatic children (four girls, age range: 10 to 17 years) sensitized only to Dermatophagoides pteronyssinus (Dp). Further, changes in bronchial responsiveness to inhaled methacholine following LAR were examined by measuring PC20FEV1 methacholine after 24, 48, and 72 hours. We carried out two carefully controlled allergen challenges with the same allergen dose within 4 to 6 weeks, at least 3 weeks apart, in each subject. On each study day, a bronchial challenge with methacholine was performed before and at different intervals after LAR. We found that EAR (maximal % fall in FEV1 within the 1st hour) measured on two different days was highly reproducible (37.8% +/- 8.9 and 38.7% +/- 12.1; CR: 12.1; Ri: 0.92; CoV: 15.1). Late asthmatic response (maximal % fall in FEV1 between 2nd and 12th hour) was also highly reproducible (47.5% +/- 12.4 and 46.1% +/- 13.4; CR: 10.1; Ri: 0.96; CoV: 10.1). All patients showed increases in nonspecific bronchial responsiveness to methacholine after LAR. Geometric mean PC20 M measured before the two allergen challenges was 0.609 mg/mL and 0.620 mg/mL, respectively. These values significantly decreased 24, 48, and 72 hours after LAR (after 1st allergen challenge: 0.086, 0.116, and 0.295 mg/mL; after 2nd allergen challenge: 0.075, 0.141, and 0.263 mg/mL). Ratio changes in PC20 methacholine (pre-allergen PC20 methacholine/lowest postallergen PC20) were highly reproducible (Ri: 0.95). We concluded that bronchial response to allergen challenge and the associated increase in responsiveness to methacholine are highly reproducible in well selected asthmatic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium channel autoantibodies in myasthenic syndrome and small cell lung cancer.

Lambert-Eaton myasthenic syndrome (LEMS) is one of the neurologic paraneoplastic syndromes often found in patients with lung cancer. It is characterized by a generalized deficit of neurotransmitter release. Patients with small cell lung cancer (SCLC) in particular may develop LEMS, and SCLC is very often detected in patients affected by LEMS. LEMS is an autoimmune disease, and autoantibodies that interfere with neurotransmitter release by binding to presynaptic voltage-operated calcium channels (VOCCs) have been found in sera of patients with LEMS. Both human neuronal and SCLC cell lines express omega-conotoxin-sensitive VOCCs, and autoantibodies from patients affected by LEMS can precipitate these channels. We have now screened a large population of patients and control subjects in order to define the specificity and sensitivity of the anti-VOCC antibody assay. We have tested sera from 52 patients with LEMS with and without SCLC; 32 sera from patients with SCLC without LEMS, 31 from patients with non-SCLC, 34 from patients with inflammatory lung diseases, 17 from patients with other neurologic disorders, and 48 from healthy control subjects. We have found that a positive result with this radioimmunoassay is highly specific for LEMS, with or without SCLC, when the antibody titer is higher than 14.21 pM. Anti-VOCC antibodies have also been found in about 40% of patients with SCLC without LEMS, but they were absent in all the other populations tested. We can conclude that this serologic assay is a very useful aid in the diagnosis of LEMS, and it might be useful also for the early diagnosis of SCLC.

Effect of inhaled disodium cromoglycate and nedocromil sodium on propranolol-induced bronchoconstriction.

We conducted a randomized, double-blind, placebo-controlled study on the effect of disodium cromoglycate (DSCG) and nedocromil sodium (NED) on propranolol-induced bronchoconstriction (PIB) in 12 asthmatic subjects 10 to 53 years of age. Placebo (saline solution) and active drugs (10 mg) were aerosolized 30 minutes before bronchoprovocation with inhaled propranolol. Bronchial response to propranolol was expressed as the cumulative dose provoking a 20% fall in FEV1 (PD20P) and given in mumol. Reproducibility of PD20P was estimated before and after the days of study. PD20P varied within two doubling doses. Disodium cromoglycate and NED had no significant effect on baseline lung function. Although, geometric mean PD20P values (+/- GSEM) recorded after DSCG (7.24 mumol +/- 1.31) and after NED (9.22 mumol +/- 1.26) were higher than values recorded after placebo (6.55 mumol +/- 1.31), these differences were not statistically significant. A greater than 2-fold increase in PD20P was noted after NED in three subjects and in one subject after DSCG. We conclude that both DSCG and NED only modestly alter PIB, with some between subject differences.

Bronchial responsiveness to inhaled propranolol in asthmatic children and adults.

Inhaled propranolol (P) was administered to a population which included asthmatic children (30 subjects) and adults (43 subjects): 1) to investigate the determinants of induced bronchial response; 2) to examine the relationship with treatment requirements; 3) to determine the relationship with responsiveness to methacholine (M) and ultrasonically nebulized distilled water (UNDW) (50 subjects); and 4) to establish the short-term repeatability of bronchial response to propranolol compared with methacholine (22 subjects). Bronchial response to propranolol and methacholine was expressed as the cumulative provocative dose (PD20 in mumol) and responsiveness to UNDW as the provocative output (PO20 in ml.min-1) producing a 20% fall in forced expiratory volume in one second (FEV1). Response to propranolol was significantly related to the degree of responsiveness to methacholine, but not to age, gender, presence of atopy, age at asthma onset, or baseline FEV1. PD20P was measurable in all but three subjects. A significant difference in mean PD20M but not in PD20P was found between subjects requiring more anti-asthmatic treatments compared to those without therapy. The difference between geometric mean PD20P and geometric mean PD20M was 14.1. PO20UNDW was measurable in only 21 out of 50 subjects. Both PD20P and PD20M were significantly lower in responders to UNDW than in nonresponders. Reproducibility of PD20P was comparable to that of PD20M (coefficients of repeatability: 1.17 and 1.09). We conclude that bronchial responsiveness to propranolol is safely measurable in most children and adults with asthma. Repeatability of bronchial response to propranolol is comparable to that of methacholine. Moreover, responsiveness to propranolol is not a predictor of treatment requirement.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchial inflammation in mite-sensitive asthmatic subjects after 5 years of specific immunotherapy.

We examined the pattern and degree of the inflammatory process in bronchial biopsy specimens taken by fiberoptic bronchoscopy in eight asthmatic subjects (two women aged 19-38 years) after 5 years of specific immunotherapy (SIT) to mite extracts (SIT group). At the time of study, they received a maintenance dose of mite-extracts (last subcutaneous administration 3 weeks before bronchoscopy). Results were compared with those found in eight matched mite-sensitive subjects with stable asthma (two women aged 19-36 years; non-SIT group) and in eight healthy individuals (four women aged 22-29 years; control group). Bronchial biopsy specimens were fixed in periodate-lysine-paraformaldehyde, embedded in glycol methacrylate, and stained with hematoxylin-eosin and 2% toluidine blue. Number of eosinophils, mast cells, and total nucleated cells were counted separately in the epithelium and lamina propria by light microscopy and expressed as cells/high power field. Within the epithelium, eosinophil and mast cell counts in SIT and non-SIT groups were significantly higher compared to controls, whereas total cell counts were not statistically different. Within the lamina propria, total cell count in SIT and non-SIT groups was significantly higher compared with the control group, whereas mast cells were similar. The number of eosinophils in both SIT and non-SIT groups was higher compared with controls; however this reached statistical significance only in SIT-groups. Comparison between the two groups of asthmatics did not show any significant difference for any cell counts.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of inhaled furosemide and torasemide on bronchial response to ultrasonically nebulized distilled water in asthmatic subjects.

Inhaled furosemide has been shown to reduce the bronchoconstriction induced by several indirect stimuli, including ultrasonically nebulized distilled water (UNDW). Because the protective effect could be due to the inhibition of the Na(+)-2Cl(-)-K+ cotransport system of bronchial epithelium, we have compared the protective effect of inhaled furosemide with that of inhaled torasemide, a new and more potent loop diuretic, on UNDW-induced bronchoconstriction in a group of 12 asthmatic subjects. UNDW challenge was performed by constructing a stimulus-response curve with five increasing volume outputs of distilled water (from 0.5 to 5.2 ml/min) and the bronchial response expressed as the provocative output causing a 20% fall in FEV1 (PO20UNDW). On different days, each subject inhaled an equal dose (28 mg) of furosemide and torasemide in a randomized, double-blind, placebo-controlled study 5 min prior to an UNDW challenge. Furosemide and torasemide had no significant effect on resting lung function. The geometric mean value of PO20UNDW measured after placebo was 1.73 ml/min. This was significantly lower than that recorded after furosemide (4.25 ml/min; p < 0.025), but not after torasemide (3.05 ml/min; p = 0.07). Inhaled furosemide totally blocked bronchial response to UNDW in five subjects. In two of five subjects the response was also blocked by inhaled torasemide. A remarkable increase in diuresis was noted only after torasemide in most subjects. We conclude that inhaled furosemide has a better protective effect than does inhaled torasemide against UNDW-induced bronchoconstriction. However, the protective effect of furosemide is variable, with some asthmatic patients showing no change in bronchial response to UNDW.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of a new method for assessing arterial oxygen pressure, avoiding arterial blood collection.

Arterial computed PO2 (PO2 com) was computed from SaO2 ear and finger capillary pH using equations of Severinghaus and Ellis, and compared with measured arterial PaO2 in 100 patients with chronic obstructive pulmonary disease (76 men, aged 42 to 82 yr). SaO2 ear ranged from 73 to 98%. There was no significant difference between SaO2 ear and SaO2 com (calculated from PaO2 and arterial pH), nor between arterial pH and pHc (capillary blood). Mean directly measured finger capillary oxygen tension, PcO2, was lower than PaO2 by 10.1 mm Hg +/- 5.4 SD. Mean bias of (PaO2-PO2 com) was -0.22 mm Hg +/- 2.6 SD. When subdivided by range, bias, and SD of mean bias of (PaO2-PO2 com) were -0.47 mm Hg +/- 2.5 with SaO2 ear less than 95% and 0.1 mm Hg +/- 2.9 with SaO2 ear greater than 95%. We conclude that PaO2 may be reliably computed from SaO2 ear and capillary pH when SaO2 ear is less than 98%.

Cutaneous response to intradermal histamine in lung cancer.

Recent evidence has suggested that human neoplastic patients show decreased blood histamine levels and cutaneous responses to intradermal histamine. In this study we evaluate the skin response to intradermal injections of histamine and IgE levels in 34 male patients with lung cancer (of which 21 had metastasis) and in 16 control subjects. Analysis of our data does not reveal any difference in the areas of wheal and flare between control subjects and lung cancer patients with or without metastasis. Moreover the evaluation of the different histologic cell type of lung cancer provides the same results. In addition, the sensitivity (Histamine Threshold Concentration) and reactivity (slopes) to histamine is not statistically different. No difference is found for IgE levels between controls and cancer patients. In the light of our finding we believe that in lung cancer patients skin response to intradermal histamine is not decreased, and therefore that the hypothesis concerning the existence of H1-histamine receptor antagonist released by tumour is not confirmed.

Cancer and skin sensitivity to intradermal histamine: a preliminary report.

Any meaningful relationship of histamine concentrations, serum IgE concentrations, and the prevalence of cancer is unproven. Several reports indicate that tumor growth is associated with an increased synthesis of histamine. Others demonstrate decreased blood histamine levels and reduced cutaneous response to intradermal histamine in patients with solid malignant tumors. We have evaluated skin sensitivity to intradermal histamine injection, and IgE levels in cancer patients either with or without metastasis. Our data reveal no differences for histamine-induced wheal and flare areas between normal subjects and patients with neoplastic disease (with or without metastasis). In addition serum IgE concentrations were not statistically different. Skin sensitivity to intradermal histamine is not decreased in patients with cancer.

Effect of salbutamol on potassium influx in erythrocytes of allergic subjects and investigation of beta 2 receptor autoantibodies.

Recent experimental and clinical reports have demonstrated that beta-adrenergic blockade impairs and beta-adrenergic stimulation enhances in vivo extrarenal potassium uptake in man. In some allergic patients extrarenal potassium disposal in vivo was reduced compared with normal subjects. In the present study we report that in vitro salbutamol induced potassium uptake by red blood cells may be reduced in some atopic patients. By using a ligand binding assay on cultured human A431 cells, we tried to determine whether in the sera of these atopic subjects there could be anti beta-adrenergic receptor autoantibodies. The results suggest that the observed reduced response to salbutamol of atopics' red blood cells does not depend on autoantibody activity.