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PubMed1997

Influence of inhaled nitric oxide on systemic flow and ventricular filling pressure in patients receiving mechanical circulatory assistance.

BACKGROUND: In patients with left ventricular (LV) dysfunction, inhaled nitric oxide (NO) decreases pulmonary vascular resistance (PVR) but causes a potentially clinically significant increase in left atrial pressure (LAP). This has led to the suggestion that inhaled NO may reach the coronary circulation and have a negative inotropic effect. This study tested an alternative hypothesis that LAP increases because of volume shifts to the pulmonary venous compartment caused by NO-induced selective pulmonary vasodilation. METHODS AND RESULTS: The Thermo Cardiosystems Heartmate is an LV assist device (LVAD) that can be set (by controlling pump rate) to deliver fixed or variable systemic blood flow. Eight patients (between 1 and 11 days after LVAD implantation) were administered inhaled NO (20 and 40 ppm for 10 minutes), and LAP, systemic flow, and pulmonary arterial pressure were measured in both fixed and variable pump flow modes. In both modes, inhaled NO lowered PVR (by 25 +/- 6% in the fixed mode, P < .001, and by 21 +/- 5% in the variable mode, P < .003). With fixed pump flow, LAP rose from 12.5 +/- 1.2 to 15.1 +/- 1.4 mm Hg (P < .008). In the variable flow mode, LAP did not increase and the assist device output rose from 5.3 +/- 0.3 to 5.7 +/- 0.3 L/min (P < .008). CONCLUSIONS: A selective reduction in PVR by inhaled NO can increase LAP if systemic flow cannot increase. These data support the hypothesis that with LV failure, inhaled NO increases LAP by increasing pulmonary venous volume and demonstrate that inhaled NO has beneficial hemodynamic effects in LVAD patients.

Administration, Inhalation↗
PubMed1994

Postallergen inhaled budesonide reduces late asthmatic response and inhibits the associated increase of airway responsiveness to methacholine in asthmatics.

To determine whether inhaled budesonide given after allergen inhalation challenge inhibits the late asthmatic response (LAR) and/or the associated increase of airway responsiveness to methacholine, we performed a double-blind randomized cross-over study in 12 adult asthmatics (eight male, four female; mean age, 20.3 yr; range, 18 to 29 yr) sensitized to Dermatophagoides pteronyssinus (DP) previously shown to develop early and late asthmatic response to allergen challenge with DP. On different days each subject was randomized to receive budesonide 800 micrograms by Turbuhaler or placebo, given three times; (1) after allergen inhalation, after the onset of LAR, when FEV1 had fallen by > or = 15%; (2) 2 h later; (3) 4 h later. Airway responsiveness to methacholine was measured before allergen challenge at 8 to 10 h from allergen inhalation and 24 h after the allergen inhalation. Inhaled budesonide significantly reduced the LAR induced by allergen (maximal % fall in FEV1, delta FEV1%: -23 +/- 6% with budesonide versus -38 +/- 9% with placebo; p < 0.001) and inhibited the associated increase of airway responsiveness (geometric mean of PD20FEV1 methacholine: 0.047 mg after budesonide versus 0.033 mg after placebo at 8 to 10 h, p < 0.05; 0.119 mg after budesonide versus 0.062 mg after placebo at 24 h, p < 0.01). These results suggest that inhaled budesonide may not only prevent but also reduce the late asthmatic response induced by allergen and that it might also be considered in the treatment of exacerbation of asthma.

Administration, Inhalation↗
PubMed1995

Improvement in VA/Q distributions during inhalation of nitric oxide in pigs with methacholine-induced bronchoconstriction.

Effects of nitric oxide (NO) and aerosolized terbutaline inhalation on ventilation-perfusion (VA/Q) distributions were determined during methacholine-induced bronchoconstriction in nine mechanically ventilated pigs. Animals inhaled, in random order, zero, 20, and 80 parts per million (ppm) of NO or aerosolized terbutaline. Inhalation of either 20 ppm NO or terbutaline produced similar reduction in pulmonary resistance and increase in lung compliance. Bronchodilation was most pronounced during inhalation of 80 ppm NO. NO inhalation increased PaO2 from 65 +/- 4 to 90 +/- 5 (20 ppm NO) and 104 +/- 6 mm Hg (80 ppm NO) (p < 0.05), and oxygen delivery (DO2) from 484 +/- 49 to 565 +/- 25 (20 ppm NO) and 619 +/- 43 ml/kg/min (80 ppm NO) (p < 0.05) compared with control. Aerosolized terbutaline did not increase PaO2 and DO2. NO inhalation accounted for a decrease in blood flow to shunt units (20 ppm NO: 14 +/- 1%, 80 ppm NO: 19 +/- 2%; p < 0.05) and an increase in the perfusion of normal VA/Q units (20 ppm NO: 12 +/- 1%, 80 ppm NO: 18 +/- 1%; p < 0.05). Perfusion of shunt and normal VA/Q units was similar in the absence of NO inhalation with and without aerosolized terbutaline. Pulmonary vascular resistance decreased from 510 +/- 55 to 332 +/- 22 dyn.s/cm5 with 20 ppm NO (p < 0.05) and to 329 +/- 41 dyn.s/cm5 with 80 ppm NO (p < 0.05) but did not change with terbutaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1996

Inhaled nitric oxide. A bronchodilator in mild asthmatics with methacholine-induced bronchospasm.

Nitric oxide (NO) reduces airway tone in the methacholine-treated guinea pig. We examined whether low levels of inhaled NO gas would relax airway smooth muscle tone in patients with mild asthma subjected to methacholine-induced bronchospasm. Thirteen adult volunteers with mild asthma inspired increasing concentrations of methacholine until their baseline forced expiratory volume in one second (FEV1, 3.29 +/- 0.17 L, mean +/- SEM) decreased by > or = 20% (2.33 +/- 0.18 L, p < 0.01). Thereafter, they sequentially inhaled 100 parts per million (ppm) NO, 40% O2; 40% O2; and 100 ppm NO, 40% O2 while spirometry was performed. Subsequent inhalation of isoproterenol returned the FEV1 levels to baseline. Inhaling 100 ppm NO increased FEV1 to 2.66 +/- 0.18 L (p < 0.01), and this increase was maintained after NO was discontinued. FEV1 did not change during the second period of NO inhalation. Similar results were observed for vital capacity, but no significant effect was noted on forced expiratory flow at 25% of vital capacity or peak expiratory flow. Subjects were then divided into a responder subgroup, which showed a mean increase in FEV1 after initial NO inhalation of 560 +/- 150 ml, and a nonresponder subgroup, which showed a mean increase in FEV1 of 129 +/- 29 ml. Our data suggest that inhalation of nitric oxide by patients with mild asthma with methacholine-induced bronchospasm results in a minor but significant relaxation of airway tone.

Administration, Inhalation↗
PubMed1997

Combined inhalation of nitric oxide and oxygen in chronic obstructive pulmonary disease.

Inhaled nitric oxide (NO) has been shown to reduce the mean pulmonary artery pressure (mPAP) and to improve PaO2 in patients with acute respiratory failure undergoing oxygen (O2) therapy. However, inhaled NO reduced pulmonary hypertension without improving PaO2 in patients with chronic obstructive pulmonary disease (COPD). This study was intended to compare the hemodynamic and gas exchange responses during inhalation of NO or O2 with those observed during the combined inhalation of NO and O2 in 10 spontaneously breathing COPD patients. Hemodynamic and blood gas parameters were measured after breathing: (1) room air; (2) NO added to room air; (3) O2 (1 L/min); or (4) NO and O2. During inhalation of 2 ppm NO added to room air, the mPAP (23.1 +/- 2.5 versus 20.6 +/- 2.2 mm Hg) and the pulmonary vascular resistance (PVR) (434 +/- 70 versus 378 +/- 50 dyne s/cm5) were significantly (p < 0.05) lower than those measured with room air. However, the values of PaO2 did not improve. The combined inhalation of NO and O2 was associated not only with a significant (p < 0.05) decrease of mPAP (21.4 +/- 2.3 versus 19.7 +/- 1.8 mm Hg) and PVR (431 +/- 72 versus 370 +/- 44 dyne s/cm5), but also with a remarkable improvement (p < 0.05) in the values of PaO2 (91.4 +/- 6.6 versus 111.5 +/- 7.8 mm Hg) as compared with values obtained during the inhalation of O2 alone. These findings suggest that combined therapy with NO and O2 may constitute an alternative approach to treating patients with COPD and pulmonary hypertension.

Administration, Inhalation↗
PubMed1997

Efficacy of inhaled fluticasone propionate in asthma results from topical and not from systemic activity.

The objective of this study was to determine whether the therapeutic benefits of inhaled fluticasone propionate are mediated through topical or systemic effects. Two hundred seventy-four patients with asthma receiving beclomethasone dipropionate or triamcinolone acetonide during a 2-wk, single-blind, run-in period were randomized to inhaled fluticasone propionate powder 100 or 500 micrograms twice daily, oral fluticasone propionate 20 mg once daily, or placebo during a 6-wk treatment period. Patients receiving inhaled fluticasone propionate had a significantly greater probability of remaining in the study over time compared with patients receiving oral fluticasone propionate or placebo (p = 0.001). FEV1 and PEF rates at end point were significantly higher with inhaled fluticasone propionate treatment regimens than with oral fluticasone propionate (with the exception of PEF rates for inhaled fluticasone propionate 100 micrograms) or placebo treatments (p < or = 0.004). Systemic exposure to fluticasone propionate as assessed by trough plasma concentrations and/or 12-hr plasma concentration area under the curve analyses (AUC12) was higher with the oral fluticasone propionate than with the two inhaled fluticasone propionate treatment groups. The results of this study suggest that the therapeutic benefits of inhaled fluticasone propionate are mediated through topical effects in the lungs and not through systemic effects.

Administration, Inhalation↗
PubMed1998

Inhaled corticosteroids and the prevention of readmission to hospital for asthma.

Despite the proven efficacy of inhaled corticosteroids in reducing airway inflammation and their increasing use for the treatment of asthma since the mid 1980s, hospitalization for asthma has been increasing in frequency in several countries. Only few studies, reporting contradictory results, have investigated the role of inhaled corticosteroids in the prevention of hospitalizations for asthma. Using a cohort of 2,059 hospitalized asthmatic patients between 5 and 54 yr of age, we estimated the effectiveness of inhaled corticosteroids in preventing a readmission to hospital for asthma as a function of the duration of therapy. The cohort was selected from the databases of Saskatchewan Health from 1977 to 1993. The rate ratio (RR) of a readmission for asthma varied with duration of regular therapy with inhaled corticosteroids. During the first 15 d of regular therapy, users of inhaled corticosteroids were as likely as nonusers of these medications to be readmitted for asthma with a RR of 1.2 (95% CI: 0.8-1.8). Subjects treated regularly with inhaled corticosteroids for at least 16 d and as long as 6 mo were 40% less likely to be readmitted for asthma (RR = 0.6; 95% CI: 0.4-0.9), while after 6 mo of regular treatment the protective effect disappeared (RR = 1.3; 95% CI: 0.7-2.4). We conclude that regular therapy with inhaled corticosteroids can substantially reduce the risk of a readmission for asthma after only 15 d of use. Confounding by severity appears as the most likely explanation for the disappearance of the beneficial effect after 6 mo of regular therapy.

Administration, Inhalation↗
PubMed1999

Systemic effects of inhaled fluticasone propionate and budesonide in adult patients with asthma.

We assessed the systemic effects of budesonide (BUD) and fluticasone propionate (FP) in 23 patients with asthma, using a double-blind, placebo-controlled, double-dummy, and cross-over design. The following five treatments were given in a randomized order for 1 wk with a washout period in between of 2 wk: (1) placebo; (2) FP, 200 micrograms twice a day, inhaled from a Diskhaler; (3) FP, 1,000 micrograms twice a day, inhaled from a Diskhaler; (4) BUD, 200 micrograms twice a day, inhaled from a Turbuhaler; and (5) BUD, 800 micrograms twice a day, inhaled from a Turbuhaler. The primary variable was the area under the curve of serum cortisol versus time (AUC0-20), derived from serum samples taken every 2 h over a 20-h period following the last evening dose at 10:00 P.M. The lower doses of BUD and FLU did not cause any adrenal suppression. Compared with placebo, however, FP (1, 000 micrograms, twice daily and BUD (800 micrograms, twice daily) decreased the AUC0-20 by 34 and 16%, respectively. Fluticasone (1,000 micrograms, twice daily) was more suppressive than BUD (800 micrograms, twice daily) (p = 0.0006). The FEV1, measured the morning after the last inhalation, was significantly higher after the active treatments, compared with placebo (p < 0.02), but did not differ between all active treatments. We conclude that high doses of BUD and FP (in particular the latter), inhaled via their respective dry powder inhalers for 1 wk, result in a measurable systemic activity in patients with asthma.

Administration, Inhalation↗
PubMed1999

Variable airway responsiveness to inhaled lipopolysaccharide.

Individuals exposed to inhaled endotoxin (lipopolysaccharide [LPS]) can develop airway symptomatology and exacerbations of asthma. Moreover, among those occupationally exposed to organic dusts, the progression of airflow obstruction is related to the endotoxin concentration in the bioaerosol. Not everyone exposed to high concentrations of LPS develops these problems. To determine whether individuals express a differential response to inhaled LPS, we challenged 72 healthy volunteers with increasing doses of LPS. Airflow was assessed after each dose and the protocol was terminated for decline in FEV1 >/= 20%. Marked differences in the response to inhaled LPS were observed: eight "sensitive" subjects had at least 20% decline in their FEV1 after inhaling 6.5 micrograms or less of LPS, whereas 11 "hyporesponsive" subjects maintained an FEV1 >/= 90% of their baseline even after inhaling 41.5 micrograms of LPS. Serial testing demonstrated that the response to inhaled LPS is reproducible. Sensitive subjects were more commonly female and hyporesponsive subjects were more often male (p = 0.016). Peripheral blood monocytes from hyporesponsive subjects, compared with sensitive subjects, released less interleukin (IL)-6 and IL-8. These findings demonstrate that an LPS phenotype can be reproducibly elicited in humans, which creates an opportunity to identify genes involved in this response to inhaled LPS.

Administration, Inhalation↗
PubMed2001

Short-term effects of inhaled nitric oxide and prone position in pulmonary and extrapulmonary acute respiratory distress syndrome.

Inhaled nitric oxide (NO) and prone position (PP) are frequently used in the treatment of acute respiratory distress syndrome (ARDS). We compared the gas exchange and hemodynamic effects induced by the combination of NO inhalation and PP in patients with ARDS and analyzed whether or not pulmonary (Pu) and extrapulmonary (Epu) ARDS patients behave differently. Eight Pu and seven Epu ARDS patients were studied in four situations: supine position (SP); SP with NO inhalation at 5 ppm (SP + NO); PP; and PP with NO inhalation (PP + NO). In comparison with SP, NO inhalation and PP induced significant increases in Pa(O(2))/FI(O(2)) (from 106 +/- 58 in SP to 131 +/- 69 mm Hg in SP + NO, p = 0.01, and to 184 +/- 67 mm Hg in PP, p < 0.001). Pu and Epu ARDS showed a similar improvement in Pa(O(2))/FI(O2) with PP. Only Pu ARDS patients showed a significant increase (p < 0.001) in oxygenation induced by NO inhalation from 81 +/- 45 to 100 +/- 50 mm Hg in SP, and from 146 +/- 53 to 197 +/- 98 mm Hg in PP. In conclusion, PP is associated with a marked improvement in oxygenation, irrespective of the causes of ARDS, and additive effects of NO inhalation are mainly seen in patients with Pu ARDS.

Administration, Inhalation↗
PubMed2001

Inhaled corticosteroids and the risk of mortality and readmission in elderly patients with chronic obstructive pulmonary disease.

There is considerable controversy concerning the utility of inhaled corticosteroids for the long-term treatment of patients with COPD. Recent studies have suggested that although inhaled corticosteroids do not alter the rate of decline in lung function, they may reduce airway hyperresponsiveness, decrease the frequency of exacerbations, and slow the rate of decline in the patients' health status. The relationship between inhaled corticosteroids and subsequent risk of hospitalization or mortality remains unknown. We therefore conducted a population-based cohort study using administrative databases in Ontario, Canada (n = 22,620) to determine the association between inhaled corticosteroid therapy and the combined risk of repeat hospitalization and all-cause mortality in elderly patients with COPD. Patients who received inhaled corticosteroid therapy postdischarge (within 90 d) had 24% fewer repeat hospitalizations for COPD (95% confidence interval [CI], 22 to 35%) and were 29% less likely to experience mortality (95% CI, 22 to 35%) during 1 yr of follow-up after adjustment for various confounding factors. This cohort study has suggested that inhaled corticosteroid therapy is associated with reduced COPD-related morbidity and mortality in elderly patients. Although not definitive, because of the observational nature of these findings, these data provide a compelling rationale for a large randomized trial to determine the effect of inhaled corticosteroids on COPD-related morbidity and mortality.

Administration, Inhalation↗
PubMed1989

Tachyphylaxis to systemic but not to airway responses during prolonged therapy with high dose inhaled salbutamol in asthmatics.

High doses of inhaled salbutamol produce substantial improvements in airway response in patients with asthma, and are associated with dose-dependent systemic beta-adrenoceptor responses. The purpose of the present study was to investigate whether tachyphylaxis occurs during prolonged treatment with high dose inhaled salbutamol. Twelve asthmatic patients (FEV1, 81 +/- 4% predicted), requiring only occasional inhaled beta-agonists as their sole therapy, were given a 14-day treatment with high dose inhaled salbutamol (HDS), 4,000 micrograms daily, low dose inhaled salbutamol (LDS), 800 micrograms daily, or placebo (PI) by metered-dose inhaler in a double-blind, randomized crossover design. During the 14-day run-in and during washout periods, inhaled beta-agonists were withheld and ipratropium bromide was substituted for rescue purposes. At the end of each 14-day treatment, a dose-response curve (DRC) was performed, and airway (FEV1, FEF25-75) chronotropic (HR), tremor, and metabolic (K, Glu) responses were measured at each step (from 100 to 4,000 micrograms). Treatment had no significant effect on baseline values. There were dose-dependent increases in FEV1 and FEF25-75 (p less than 0.001), and pretreatment with HDS did not displace the DRC to the right. DRC for HR (p less than 0.001), K (p less than 0.001), and Glu (p less than 0.005) were attenuated after treatment with HDS compared with PI. There were also differences between HDS and LDS for HR (p less than 0.001) and Glu (p less than 0.05) responses. Frequency and severity of subjective adverse effects were also reduced after HDS: tremor (p less than 0.001), palpitations (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1990

Effects of inhaled PAF in humans on circulating and bronchoalveolar lavage fluid neutrophils. Relationship to bronchoconstriction and changes in airway responsiveness.

We have compared the effect of inhaled platelet activating factor (PAF) on circulating neutrophils with its ability to induce bronchoconstriction and bronchial hyperresponsiveness in humans. Human volunteers inhaled PAF, given as six successive inhalations 15 min apart, followed by bronchoalveolar lavage (BAL) 4 h later. The mean density and volume of circulating neutrophils were measured by metrizamide gradients and flow cytometry, respectively. PAF caused a decrease in Vp20 of 38.2 +/- 4.5% at 5 min after the first inhalation (p less than 0.001). This was associated with a fall in the peripheral blood neutrophil count from 3.15 +/- 0.3 to 1.1 +/- 0.3 x 10(6) per ml (p less than 0.001), followed by a rebound neutrophilia (p less than 0.01). The mean density of peripheral blood neutrophils fell significantly at 15 min (p less than 0.02), with a return to baseline values despite further PAF inhalations; this was associated with an increase in neutrophil volume (n = 4; p less than 0.05). The numbers of neutrophils (x 10(5] in BAL fluid after PAF were significantly greater than after inhalation of lyso-PAF: 7.1 +/- 1.4 (n = 7) versus 1.3 +/- 0.3 (n = 5, p less than 0.01); eosinophil counts did not change significantly. The PC40 (the concentration of methacholine needed to cause a fall in Vp30) decreased from 17.1 (GSEM 1.40) to 8.7 (1.44) mg/ml (n = 12, p less than 0.02) 3 days after PAF. Inhaled lyso-PAF was inactive in all these respects.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1990

Effects of inhaled leukotriene D4 and platelet-activating factor on airway reactivity in normal subjects.

Inflammatory mediators such as platelet-activating factor (PAF) and the sulfidopeptide leukotrienes (LT) may contribute to airway hyperreactivity and asthma. PAF has been reported to produce bronchoconstriction and a sustained increase in airway reactivity when inhaled by normal subjects. Leukotrienes produce bronchoconstriction in both normal and asthmatic subjects, but whether they increase airway reactivity is unclear. Before initiating studies to determine how these bioactive mediators influence airway function, we sought to confirm that PAF increases airway reactivity and identify whether one of the sulfidopeptide leukotrienes, LTD4, has a similar effect. Eight normal male subjects inhaled saline and increasing concentrations of either histamine (0.1 to 50 mg/ml), PAF (1 to 1,000 micrograms/ml), or LTD4 (1 to 500 micrograms/ml) on separate days, at least 1 wk apart, until specific airway conductance (SGaw) decreased 50% or the maximal concentration was reached. After inhaling the test substance, methacholine (MCh) challenges were performed at 6 h, at 1, 3, and 7 days, and weekly thereafter until airway reactivity (measured as the MCh concentration that decreased SGaw 35% [PC35SGaw]) normalized. The four postsaline MCh challenges (6 h to 7 days) were used to determine the 95% confidence interval for PC35SGaw (in each subject) and identify significant changes in airway reactivity after inhaling each test substance. Airway reactivity did not change after inhaling histamine. After inhaling PAF, six of eight subjects developed increased airway reactivity, which was maximal at 1 day and persisted for 14 days in three. After inhaling LTD4, six of eight subjects also developed increased airway reactivity, which was maximal at 7 days and persisted for 14 days in two.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1990

Inhaled salmeterol and salbutamol in asthmatic patients. An evaluation of asthma symptoms and the possible development of tachyphylaxis.

Salmeterol (SM) is a new beta 2-adrenoceptor agonist for inhaled use that has been shown to produce long-lasting bronchodilation in asthmatic patients. In the present study, evaluating efficacy and possible development of tachyphylaxis after SM, 12 patients with stable asthma were included after the demonstration of reversibility in FEV1 of at least 15% to 200 micrograms salbutamol (SB) or 20% to 500 micrograms SB. At inclusion all patients were receiving treatment with inhaled beta 2-agonists, and 11 of the 12 patients were also receiving inhaled corticosteroids. The patients were treated for two 2-wk periods with either inhaled SM 50 micrograms twice a day or SB 200 micrograms four times a day, following a double-blind, double-dummy, randomized design. The treatment periods were separated by a washout period of 1 wk. Dose-response curves to inhaled SB were obtained the day before and the day after each treatment period. On each of these days, basal FEV1, tremor, heart rate, and blood pressure were recorded and were then followed after the inhalation of 100 + 300 + 900 micrograms SB to obtain a cumulative dose-response curve. During the treatment periods, as well as during the washout week after each treatment, the patients recorded their morning and evening peak expiratory flow (PEF) each day before the inhalation of the study drug. Subjective asthma symptoms were monitored by a visual analog scale after each treatment period. The dose-response curves to SB revealed no signs of a reduced response to SB after any of the treatments, but significant increases in basal FEV1 and FVC were seen after the SM period (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1991

Inhaled furosemide prevents both the bronchoconstriction and the increase in neutrophil chemotactic activity induced by ultrasonic "fog" of distilled water in asthmatics.

Inhaled furosemide has been shown to prevent bronchoconstriction induced by inhalation of ultrasonic nebulization of distilled water (UNDW) in bronchial asthma. To evaluate whether inhaled furosemide also prevents the increase in serum neutrophil chemotactic activity (NCA) observed during UNDW bronchoconstriction, we measured NCA during UNDW challenge without (control) and immediately after inhalation of furosemide (40 mg) or placebo (saline) in 10 asthmatics responsive to UNDW, in a randomized, double-blind study. NCA was assessed by measuring the maximal distance reached by neutrophils in a filter when challenged with the subject serum in a Boyden chamber ("leading front"). UNDW inhalation produced a significant increase in NCA in each subject. Gel filtration chromatography on S400 column indicated that the NCA released were 600 to 700 kD. Saline had no effect on bronchoconstriction nor on NCA increase induced by UNDW in nine patients. Furosemide did not change baseline FEV1, but it prevented bronchoconstriction and NCA increase in nine patients. In the whole group the maximal decrease in FEV1 after UNDW was -31.1%, SEM 4.7 after saline and -7.5%, SEM 5.2 after furosemide, p less than 0.001, the maximal increase in NCA after UNDW was +52.9%, SEM 9.2 after saline and +3.8%, SEM 3.1 after furosemide, p = 0.001. These results indicate that inhaled furosemide prevents both the bronchoconstriction and the NCA increase induced by UNDW inhalation in most asthmatic patients. This finding adds support to the suggestion that furosemide acts on mast cells.

Administration, Inhalation↗
PubMed1993

Potent leukotriene D4 receptor antagonist ICI 204,219 given by the inhaled route inhibits the early but not the late phase of allergen-induced bronchoconstriction.

ICI 204,219 is a potent and specific leukotriene D4 receptor antagonist that blocks both the early and late responses to allergen challenge in humans when given orally at a dose of 40 mg. Here we report our findings with an inhaled formulation of ICI 204,219 against allergen-induced bronchoconstriction. A group of 10 atopic subjects (mean age 25.6 +/- 4.2; 6 females; FEV1 > 90% of predicted; on inhaled beta 2-agonists only) were studied on 2 separate days 2 to 3 wk apart. In a randomized placebo-controlled trial they inhaled eight puffs of a standard metered dose inhaler containing either ICI 204,219 (200 micrograms/puff, total dose 1,600 micrograms) or propellant alone. They underwent bronchial allergen challenge 30 min later using a single concentration of allergen previously shown to lower the FEV1 by > or = 15%. FEV1 was monitored hourly for 10 h, and urine was collected for LTE4 determination. Inhalation of ICI 204,219 was well tolerated, with no adverse clinical or biochemical effects. There was no significant effect of ICI 204,219 inhalation on basal airway caliber (change in FEV1 30 min after inhalation was -149 +/- 67 ml after placebo versus 3 +/- 38 ml after ICI 204,219; p = 0.08). The early response to allergen was significantly inhibited by ICI 204,219 (the maximum fall in FEV1 was -21.2 +/- 6.1% after ICI 204,219 compared with -38.8 +/- 6.5% on placebo; p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed2002

Increasing concentration of inhaled saline with or without amiloride: effect on mucociliary clearance in normal subjects.

Mucociliary clearance is determined by ciliary activity and rheology of airway surface liquid. To test the hypothesis that mucociliary clearance would increase after inhalation of an osmotically active agent that would increase the volume of airway surface liquid, we measured mucociliary clearance in 16 normal subjects after inhalation of varying tonicities of saline alone, and after pretreatment with a Na+ channel blocker (amiloride). Subjects inhaled vehicle (0.12% saline) or amiloride, followed by inhalation of 0.12, 0.9, or 7% saline. Subsequently, mucociliary clearance rates were measured by gamma scintigraphy of inhaled 99mTc Fe2O3. Mucociliary clearance of whole and peripheral lung was increased (approximately twofold) after inhalation of increasing concentrations of saline (p < 0.04). Pretreatment with amiloride increased mucociliary clearance rates (approximately twofold) after inhalation of 0.12 and 0.9% saline (p < 0.05), but not 7% saline. The rates of mucociliary clearance by pretreatment with amiloride and 7% saline alone (approximately 1.4% per minute) approached the rapid mucociliary clearance rates (approximately 2.0% per minute) reported in systemic pseudohypoaldosteronism, which has loss-of-function mutations of the epithelial Na+ channel and an increased volume of airway surface liquid. We conclude that maneuvers that increase the volume of airway surface liquid are associated with increased rates of mucociliary clearance in normal subjects.

Administration, Inhalation↗