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PubMedDate not supplied

Exhaling a budesonide inhaler through the nose results in a significant reduction in dose requirement of budesonide nasal spray in patients having asthma with rhinitis.

Budesonide, an inhaled corticosteroid is used routinely in the treatment of bronchial asthma and rhinitis. Although inhaled corticosteroids in therapeutic doses are unlikely to result in systemic side effects, there is as yet skepticism about their routine and prolonged use. The aim of this study was to determine whether budesonide inhalation through a metered dose inhaler, when exhaled through the nose could result in a reduction in the dose requirement of budesonide metered nasal spray in patients having perennial allergic asthma with rhinitis. This study was an open, parallel, comparative, crossover trial in which 49 young patients having perennial allergic asthma with rhinitis were divided into two groups and administered either a combination of budesonide metered dose inhaler with a budesonide nasal spray or a budesonide inhaler alone, which was to be exhaled through the nose. Both groups were later crossed over and weekly symptom scores and peak nasal inspiratory flow rates were monitored during each phase of the study. Finally, patients who volunteered from both groups were instructed to note the reduction in dose requirement of budesonide nasal spray while using a budesonide inhaler and exhaling it through the nose. The results of this study reveal that when a budesonide inhaler is exhaled through the nose, it results in an improvement in symptom scores and peak nasal inspiratory flow rates, which were significantly less than those obtained in the group using both a budesonide nasal spray and a metered dose inhaler. In addition, exhaling budesonide through the nose results in a 40.1% reduction in the dose requirement of a budesonide nasal spray, which is statistically significant (p < 0.001).

Administration, Inhalation↗
PubMed2000

Toxicology and carcinogenesis studies of naphthalene (cas no. 91-20-3) in F344/N rats (inhalation studies).

UNLABELLED: Naphthalene is used as an intermediate in the synthesis of phthalic and anthranilic acids, naphthols, naphthylamines, sulfonic acid, synthetic resins, celluloid, and hydronaphthalenes; it is also used in the preparation of anthraquinone, indigo, salicylic acid, and 1-naphthyl-N-methylcarbamate insecticide. It is an ingredient in some moth repellants and toilet bowl deodorants; it is also used in veterinary medicine in antiseptics for irrigating animal wounds and as an external medication to control lice on livestock and poultry. Naphthalene was selected for study by the National Toxicology Program because previous inhalation studies with naphthalene in mice were positive and existing studies in rats were either considered inadequate or were conducted via routes other than inhalation. Male and female F344/N rats were exposed to naphthalene (greater than 99% pure) by inhalation for 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and cultured Chinese hamster ovary cells. 2-YEAR STUDY: Groups of 49 male and 49 female rats were exposed to naphthalene by inhalation at concentrations of 0, 10, 30, or 60 ppm for 6 hours plus T90 (12 minutes) per day, 5 days per week for 105 weeks. Additional groups of nine male and nine female rats were exposed to 10, 30, or 60 ppm for up to 18 months for evaluation of toxicokinetic parameters. Survival, Body Weights, and Gross Observations: The survival of all exposed groups of male and female rats was similar to that of the chamber controls. Mean body weights of all exposed groups of males were less than those of the chamber control group throughout most of the study. Masses were observed in the nose of male and female rats. These masses frequently partially occluded the nasal passages or obliterated the normal architecture of the nasal turbinates. Pathology Findings: The incidences of neuroblastoma of the olfactory epithelium, a rare neoplasm, occurred with positive trends in males and females. Because this neoplasm did not occur in chamber control rats or in male rats exposed to 10 ppm and because this neoplasm has not been seen in the historical chamber control rats in NTP 2-year inhalation studies, the increased incidences of neuroblastoma were considered to be related to naphthalene exposure. In males, the incidences of adenoma of the respiratory epithelium of the nose, another rare neoplasm, occurred with a positive trend and were significantly increased in all exposed groups; none occurred in the chamber controls. In females, these neoplasms occurred in the 30 and 60 ppm groups but not in the chamber control or 10 ppm groups. Because these neoplasms did not occur in the chamber controls and have not been observed in the historical chamber control rats in NTP 2-year inhalation studies, the incidences of nasal adenoma were considered to be related to naphthalene exposure. Increased incidences of nonneoplastic lesions of the nose associated with exposure to naphthalene included atypical hyperplasia, atrophy, chronic inflammation, and hyaline degeneration of the olfactory epithelium; hyperplasia, squamous metaplasia, hyaline degeneration, and goblet cell hyperplasia of the respiratory epithelium; and glandular hyperplasia and squamous metaplasia. Toxicokinetic Results Model: A physiologically based toxicokinetic model was developed to characterize the disposition of inhaled naphthalene in rats. Because of its low vapor pressure and high blood-to-air partition coefficient, essentially all of the naphthalene that is absorbed into the general circulation is metabolized. At the exposure concentrations used in the 2-year study, approximately 20% to 30% of the inhaled dose was metabolized by male and female rats. Naphthalene that was not absorbed during exposure was assumed to be exhaled. The respective estimated daily doses metabolized by rats exposed to 10, 30, or 60 ppm for 6 hours (i.e., the internalized doses) are 3.6, 10.7, and 20.1 mg naphthalene/kg body weight for males and 3.9, 11.4, and 20.6 mg/kg for females. GENETIC TOXICOLOGY: Naphthalene was not mutagenic in any of four strains of Salmonella typhimurium with or without induced liver S9 enzymes. However, in cytogenetic tests with cultured Chinese hamster ovary cells, naphthalene induced significant increases in sister chromatid exchanges with and without metabolic activation (S9) and in chromosomal aberrations with S9. Naphthalene did not induce chromosomal aberrations in the absence of S9 activation. CONCLUSIONS: Under the conditions of this 2-year inhalation study, there was clear evidence of carcinogenic activity of naphthalene in male and female F344/N rats based on increased incidences of respiratory epithelial adenoma and olfactory epithelial neuroblastoma of the nose. In male and female rats, exposure to naphthalene caused significant increases in the incidences of non-neoplstic lesions of the nose.

Administration, Inhalation↗
PubMed2004

NTP technical report on the toxicology and carcinogenesis studies of Stoddard Solvent IIC (Cas No. 64742-88-7) in F344/N rats and B6C3F1 mice (inhalation studies).

UNLABELLED: Stoddard solvent (white spirit/mineral spirit) is the most widely used solvent in the paint industry. It is used as a dry cleaning agent; as an extraction, cleaning, and degreasing solvent; and as a solvent in aerosols, paints, wood preservatives, asphalt products, lacquers, and varnishes. Stoddard solvent IIC was nominated by the International Union, United Auto Workers, for carcinogenicity testing because of the large volume used in industrial and other settings. Male and female F344/N rats and B6C3F1 mice were exposed to Stoddard solvent IIC (greater than 99% pure) by inhalation for 2 weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and mouse peripheral blood erythrocytes. 2-WEEK STUDY IN RATS: Groups of five male and five female rats were exposed to Stoddard solvent IIC by inhalation at concentrations of 0, 138, 275, 550, 1,100, or 2,200 mg/m3, 6 hours per day, 5 days per week for 16 days. All rats survived to the end of the study, and mean body weights of all exposed groups were similar to those of the chamber controls. Liver weights of males exposed to 550 mg/m3 or greater and of females exposed to 275 mg/m3 or greater were increased. Minimal diffuse cytoplasmic vacuolization of hepatocytes of the liver occurred in all females exposed to 2,200 mg/m3. 2-WEEK STUDY IN MICE: Groups of five male and five female mice were exposed to Stoddard solvent IIC by inhalation at concentrations of 0, 138, 275, 550, 1,100, or 2,200 mg/m3, 6 hours per day, 5 days per week for 17 days. All mice survived to the end of the study, and mean body weights of all exposed groups were similar to those of the chamber controls. Liver weights of males and females exposed to 275 mg/m3 or greater were significantly increased. Cytomegaly of the liver occurred in all males and females exposed to 2,200 mg/m3. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were exposed to Stoddard solvent IIC by inhalation at concentrations of 0, 138, 275, 550, 1,100, or 2,200 mg/m3, 6 hours per day, 5 days per week for 14 weeks. All rats survived to the end of the study, and the final mean body weight of females exposed to 275 mg/m3 was greater than that of the chamber controls. The relative kidney, liver, and testis weights of all exposed groups of males and the absolute kidney weights of males exposed to 550 mg/m3 or greater were increased. The sperm motility of 550 mg/m3 or greater males was significantly decreased. The incidences of renal tubule granular casts were significantly increased in males exposed to 550 mg/m3 or greater, and the severities of renal tubule hyaline droplet accumulation, granular casts, and regeneration increased with increasing exposure concentration in males. The incidences of goblet cell hypertrophy of the nasal respiratory epithelium in males and females exposed to 2,200 mg/m3 were significantly increased. Sperm motility was decreased in males exposed to 550 mg/m3 or greater. 3-MONTH STUDY IN MICE: Groups of 10 male and 10 female mice were exposed to Stoddard solvent IIC by inhalation at concentrations of 0, 138, 275, 550, 1,100, or 2,200 mg/m3, 6 hours per day, 5 days per week for 14 weeks. Mean body weights of exposed groups were similar to those of the chamber controls, but liver weights of males exposed to 2,200 mg/m3 were significantly increased. The sperm motility of 2,200 mg/m3 males was significantly decreased. This reduction in sperm motility, while statistically significant, is probably of modest importance as studies in mice have found that fertility is unaffected by motility decreases of less than 40%. The incidences of hematopoietic cell proliferation of the spleen in all exposed groups of females were greater than that in the chamber controls. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to Stoddard solvent IIC by inhalation at concentrations of 0, 138 (males), 550, 1,100, or 2,200 (females) mg/m3, 6 hours per day, 5 days per week for 104 to 105 weeks. Additional groups of 10 males and 10 females were exposed to the same concentrations for 3 months for renal toxicity analyses. Survival in the top exposure concentration groups of males and females was significantly less than that of the chamber controls. Mean body weights of exposed males and females were similar to those of the chamber controls. Cell proliferation analyses were performed in the left kidney of males and females after 3 months of exposure. The mean numbers of labeled cells and the labeling indices in males exposed to 550 and 1,100 mg/m3 were significantly increased. The amount of alpha2u-globulin in the right kidney of males increased with increasing exposure concentration. Also, the incidences of granular casts and cortical tubule degeneration and regeneration were generally increased in exposed males, as was the severity of hyaline droplets. These effects did not occur in females. At 2 years, the incidences of benign and benign or malignant pheochromocytoma (combined) of the adrenal medulla occurred with positive trends in males, and the incidences in the 550 and 1,100 mg/m3 groups were significantly increased. Due to increased incidences of renal tubule hyperplasia in males at 2 years, extended kidney evaluations were conducted; a slightly increased incidence of renal tubule adenoma occurred in the 1,100 mg/m3 group. Nonneoplastic lesions related to Stoddard solvent IIC exposure occurred in the kidney of males. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed to Stoddard solvent IIC by inhalation at concentrations of 0, 550, 1,100, or 2,200 mg/m3, 6 hours per day, 5 days per week for 105 weeks. Survival of exposed mice was similar to that of the chamber controls. Mean body weights of exposed females were greater than those of the chamber controls. The incidences of hepatocellular adenoma occurred with a positive trend in females, and the incidence of multiple hepatocellular adenoma in females exposed to 2,200 mg/m3 was significantly increased. However, the incidences of hepatocellular adenoma or carcinoma (combined) and hepatocellular carcinoma alone in exposed males and females were not significantly increased. GENETIC TOXICOLOGY: Stoddard solvent IIC was tested for mutagenicity in Salmonella typhimurium strains TA97, TA98, TA100, and TA1535, with and without S9 metabolic activation enzymes; all results were negative. In vivo, the frequency of micronucleated erythrocytes was assessed in peripheral blood samples from male and female B6C3F1 mice after 3 months of inhalation exposure to Stoddard solvent IIC, and results were negative. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was some evidence of carcinogenic activity of Stoddard solvent IIC in male F344/N rats based on increased incidences of adrenal medulla neoplasms; the slightly increased incidences of renal tubule adenoma may have been related to Stoddard solvent IIC exposure. There was no evidence of carcinogenic activity of Stoddard solvent IIC in female F344/N rats exposed to 550, 1,100, or 2,200 mg/m3. There was no evidence of carcinogenic activity of Stoddard solvent IIC in male B6C3F1 mice exposed to 550, 1,100, or 2,200 mg/m3. There was equivocal evidence of carcinogenic activity of Stoddard solvent IIC in female B6C3F1 mice based on increased incidences of hepatocellular adenoma; this slight increase was associated with increased body weight in exposed females. Exposure of male rats to Stoddard solvent IIC resulted in nonneoplastic lesions of the kidney characteristic of alpha2u-globulin accumulation.

Adrenal Gland Neoplasms↗
PubMed1992

[Use of beta-agonist inhalation concomitantly with regular beclomethasone dipropionate in patients with bronchial asthma--as required or on a regular basis].

We investigated whether regular use of beta-agonist inhalation concomitantly with regular beclomethasone dipropionate (BDP) inhalation is necessary in chronic bronchial asthma. Twenty chronic asthmatic patients who were stable on regular BDP and beta-agonist inhalation were studied. After a 2 week observation period, the patients were randomly assigned to two groups. One group received BDP 400 micrograms/day (2 puffs 4 times) and beta-agonist inhalation as required for 4 weeks. This period was followed by 4 weeks of treatment with BDP 400 micrograms/day and regular beta-agonist inhalation. The other group received these treatments in the reverse order. No significant differences among the two groups were observed in attack score, ADL score, sleep score, and %PEFR. In addition, no differences were detected in these parameters between the periods of regular use of beta-agonist and the periods of use as required. The frequency of inhalation of beta-agonist during the use as required period correlated with the sleep score and difference in %PEFR between morning and night, and was significantly lower than the frequency of inhalation during the period of regular. From these results, we conclude that inhalation of beta-agonist on a regular basis is not necessary to achieve the same degree of relief of symptoms as treatment with beta 2-agonist and BDP inhalation on regular basis in patients with chronic asthma.

Administration, Inhalation↗
PubMed1991

[Inhalation chambers].

Since the last 30 years metered-dose pressurised aerosols have largely contributed to the treatment of asthma with inhaled beta-2 stimulants and corticosteroids. Two problems, however, are associated with these aerosols: (1) small amounts of active substance are deposited in the lungs and larger amounts in the mouth and pharynx; (2) aerosols are uneasy to use because of lack of coordination between actuation and inhalation and absence of apnoea at the end of inspiration. An elegant solution of these problems is the inhalation chamber: a reservoir inserted between the patient's mouth and the aerosol, which increases the lung deposition, reduces the ENT deposition and makes coordination unnecessary. The inhalation chamber is primarily indicated for patients with poor coordination. When beta-2 stimulants are inhaled the therapeutic benefit can be measured by a gain of efficacy in poor coordinators. When corticosteroids are inhaled the benefit is measured by a better local tolerance and, to some extent, by a gain in therapeutic effectiveness; the inhalation chamber here is indicated for patients with ENT complications (e.g. candidiasis, dysphonia) or for the most severe cases requiring high-dose therapy. The introduction of inhalation chamber must be regarded as an improvement in the management of asthma, taking into account the potential risk of poor compliance, and in such cases the development of powder inhalers may be envisaged.

Administration, Inhalation↗
PubMed1990

[The influence of serum theophylline concentration on the bronchodilating effect of salbutamol inhalation for bronchial asthma].

To examine the effects of serum theophylline concentration on the bronchodilating effect of beta 2-stimulant inhalated by patients with bronchial asthma, 200 micrograms-Salbutamol inhalation test was performed on 30 patients with bronchial asthma (from 17 to 71 years old, averaging 49.7; 3 mild, 15 moderate, 12 severe), who had taken theophylline at various oral doses up to 6 hours before the test. Measurements of respiratory function, serum theophylline concentration, blood pressure, pulse rate and the plasma c-AMP and c-GMP concentrations before and one hour after inhalation revealed that inhalation of 200 micrograms salbutamol significantly increased FVC, FEV1.0, PEF and plasma c-AMP (p less than 0.001). No significant change was noted in plasma c-GMP, diastolic pressure or pulse rate. Systolic pressure significantly decreased (p less than 0.05). Furthermore, no significant correlation was noted between the rates of increase (%) in FVC, FEV1.0 and PEF and those in plasma c-AMP, c-GMP and c-AMP/c-GMP in one hour after inhalation. Inaddlition no significant correlation was noted between the rates of increase in FVC, FEV1.0 and PEF one hour after inhalation and serum theophylline concentrations (0-19.3 and 0-21.5 micrograms/ml before and one hour after inhalation, respectively). The above results suggest that the bronchodilating effect of salbutamol inhalated at dose of 200 micrograms is not influenced by the serum theophylline concentration both before and at one hour after inhalation of salbutamol. The bronchodilating effect of salbutamol seems to be ascribable to an increase of intracellular c-AMP level of bronchial smooth muscle.

Administration, Inhalation↗
PubMed1991

[The role of thromboxane A2 in the development of airway responsiveness after platelet activating factor inhalation in dogs].

To determine whether thromboxane A2 (TxA2) is involved in airway hyperresponsiveness after platelet activating factor (PAF) inhalation, we studied the effect of a specific TxA2 receptor antagonist, AA-2414 on the development of airway responsiveness induced by PAF inhalation in six dogs. Airway resistance and airway responsiveness to inhaled methacholine were determined by modified Astograph (7 Hz oscillation method). PAF inhalation (1000 micrograms/ml, ten minutes) caused a significant increase of airway resistance (p less than 0.01), and the increase of airway resistance was not inhibited by pretreated AA-2414. Airway responsiveness to inhaled methacholine increased significantly 3 hr after PAF inhalation (p less than 0.01). Pretreated AA-2414 inhibited the increase of airway responsiveness significantly (p less than 0.01), but the inhibition was partial. After PAF inhalation, total cell counts, neutrophil counts, eosinophil counts and the levels of TxB2 in bronchoalveolar lavage fluid increased significantly (p less than 0.05), and these increase were not affected by pretreated AA-2414. These results suggest that TxA2 is not involved in the bronchoconstriction induced by PAF inhalation, but TxA2 plays a partial role in the development of airway responsiveness after PAF inhalation in dogs.

Administration, Inhalation↗
PubMed1986

The postoperative adverse effects of inhalational anesthetics.

Inhalational general anesthetics can contribute to postoperative morbidity (Table II). Postoperative effects of inhalational anesthetics on the central nervous system are speculative. The "toxic" effects of these agents during the postoperative period are most often an extension of their pharmacologic and physiochemical properties. Inhalational anesthetics may produce a number of varied changes in mental status after surgery such as headache, emergence excitement, and delirium. It is very important for health professionals to be aware of the risk of perioperative myocardial infarction in patients with preexisting heart disease if early detection and treatment are to occur. Relative to the common postoperative problems of atelectasis, pneumonia, and aspiration, inhalational agents may have a contributory role especially in patients with preexisting pulmonary disease. Postoperative nausea and vomiting are other common problems in which inhalational agents may have a role in their development. Although extensively investigated, suspected halothane hepatoxicity is a very rare complication if it exists at all. The renal effects of inhalational anesthetics are usually mild and transitory, although the use of methoxyflurane can produce direct nephrotoxicity. The evidence to support a clinically significant direct immunosuppressant effect of inhalational anesthetics after surgery is inconclusive. A concensus exists that any minor, short-lived effects are in all probability overshadowed by the nonspecific stress of surgery itself. By reducing this stress, anesthetics undoubtedly have a protective effect. There are probably no major mutagenic or carcinogenic effects of inhalational anesthetics under normal conditions. Inhalational anesthetics should be avoided during pregnancy because of their teratogenic potential and their effects on the uterus.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1995

Efficacy of once daily extended-release theophylline in decreasing the use of inhaled beta 2-agonists in stable, mild-to-moderate asthma patients.

BACKGROUND/OBJECTIVE: The purpose of this study was to determine whether the addition of extended-release theophylline to the daily treatment regimen of inhaled beta 2-agonist users would result in decreased use of beta 2-agonist while maintaining similar efficacy for treatment of asthma. METHODS: This was a single-blind, multicenter (six sites) study. Sixty-one patients with a history of mild-to-moderate asthma treated with inhaled beta 2-agonist were randomized to treatment with Theo-24 (anhydrous extended-release capsules) plus inhaled beta 2-agonist or placebo plus beta 2-agonist. Patients kept daily symptom diaries, measured peak flow rates, recorded puffs of inhaled beta 2-agonist, and adverse events during a 4-week treatment period. RESULTS: Fifty-five patients were included in the efficacy analysis. The primary efficacy variable in this study was the mean number of puffs (adjusted for baseline differences) of beta 2-agonist inhaled per day. In this study, the addition of theophylline to the daily regimen of inhaled beta 2-agonist for 4 weeks significantly reduced the total daily dose of inhaled beta 2-agonist at weeks 3 and 4 of treatment compared with placebo. The differences were significant at the P < .05 level. For patients in the theophylline group, the number of puffs decreased from an unadjusted mean of 9.81 at baseline to an adjusted mean of 6.78 after 4 weeks of treatment compared with 9.91 at baseline and 8.17 for the placebo group. There were no unexpected or serious adverse events. CONCLUSIONS: In this study, the addition of once daily, extended-release theophylline to the daily regimen of inhaled beta 2-agonist for 4 weeks significantly reduced the total daily dose of inhaled beta 2-agonist at weeks 3 and 4 of treatment compared with placebo, while maintaining acceptable asthma symptom scores.

Administration, Inhalation↗
PubMed1994

Inhalation steroids, some aspects and ways in the management of asthma.

Inhalation of steroid is important in the management of asthma and at present various steroids are available for inhalation. Aerosol treatment with steroids is most effective if used in several doses throughout the day. In moderately severe asthma it may be ineffective until airways are cleared by adequate oral doses. There are several methods of inhalation eg, metered dose inhalation, dry powder inhalation and nebulisation. The pressurised metered dose inhaler is widely used for its main advantage of compactness, convenience and readiness for use. Powdered inhalers are considered safe especially for use in children. No co-ordination is required by the patient in cases of administration by nebulisation. Inhaled route is preferred to systemic route because of its better therapeutic index ie, fewer side-effects for equivalent clinical effects. But poor inhalation technique is the reason for failure of aerosol steroids.

Administration, Inhalation↗
PubMed1994

Inhaled platelet-activating factor increases airway sensitivity but not maximal airway narrowing to methacholine in normal subjects.

To examine the effect of inhaled platelet-activating factor (PAF) on airway sensitivity and on maximal airway narrowing, we measured airway response to doubling concentrations of methacholine (MCh) 48 h before and 48 h after inhalation of 10, 50 and 100 micrograms of PAF in six nonatopic, nonasthmatic subjects. The forced expiratory volume in one second (FEV1) and airflow at 30 percent of vital capacity (V30) from partial forced expiration were used to assess changes in airway calibre. Inhalation of PAF caused only minor changes in FEV1. In contrast, inhalation of 100 micrograms of PAF caused a significant fall in V30 from 2.64 +/- 0.35 to 1.35 +/- 0.43 l.min-1 (p < 0.05). Two days after PAF inhalation a leftward shift of the concentration-response curve to MCh was observed. The MCh concentration causing a 20% fall in FEV1 (PC20FEV1) was 11.25 +/- 1.78 and 2.38 +/- 1.29 mg.ml-1 (geometric mean +/- GSEM; p < 0.05) before and after PAF inhalation, respectively. PAF did not affect the maximal airway response to MCh. The maximum percentage fall in FEV1 was 36.2 +/- 1.9% at baseline and 37.6 +/- 1.8% after PAF inhalation. Likewise, maximum percentage change in V30 was 72.8 +/- 3.7% at baseline and 73.6 +/- 3.4% after PAF inhalation. The results of this study show that PAF inhalation increases airway sensitivity without altering the maximal bronchoconstrictive response to MCh in normal subjects.

Administration, Inhalation↗
PubMed1994

[Effects of inhaled SDZ ISQ 844, a cyclic nucleotide phosphodiesterase isoenzyme type III/IV inhibitor, on airway responsiveness in beagles].

To evaluate the effects of inhaled SDZ ISQ 844, a selective cyclic nucleotide phosphodiesterase (PDE) isoenzyme type III/IV inhibitor and inhaled salbutamol on airway responsiveness, we studied the changes in airway responsiveness following inhalation of SDZ ISQ 844 and salbutamol in 7 beagles. Respiratory resistance and airway responsiveness to inhaled methacholine were determined by modified Astograph (7 Hz oscillation method), SDZ ISQ 844 solution (5 x 10(-4) M) and salbutamol solution (5 x 10(-5) M) were delivered as aerosols generated from a Bird nebulizer for ten minutes. After inhalation of salbutamol respiratory resistance showed a slight but significant decrease (p < 0.05). Inhaled SDZ ISQ 844 did not affect respiratory resistance. Airway responsiveness decreased significantly following inhalation of SDZ ISQ 844 and salbutamol (p < 0.02). There was no significant difference between the changes in airway responsiveness following the inhalation of SDZ ISQ 844 and salbutamol. These results indicate that inhalational administration of a selective PDE isoenzyme type III/IV inhibitor, SDZ ISQ 844 decreases airway responsiveness at dosage which does not affect the base-line respiratory resistance.

Administration, Inhalation↗
PubMed1994

Increased urinary LTE4 excretion following inhalation of LTC4 and LTE4 in asthmatic subjects.

Urinary leukotriene E4 (LTE4) increases during exacerbations of asthma and following antigen challenge. We determined whether urinary LTE4 excretion reflects sulphidopeptide leukotrienes in the airways of asthmatic patients. Urinary LTE4 concentration was measured prior to and 1.5 and 3.5 h following inhalation of bronchoconstrictive doses of leukotriene C4 (LTC4) or LTE4 in eight asthmatic subjects. Increasing doses of agonist were inhaled until a 35% fall in specific airways conductance (sGaw) was achieved. There was no significant difference between the 53 +/- 3% (mean +/- SEM) fall in sGaw following inhalation of LTC4 (63.1 ng geometric mean, GM, range 5.8-527.5 ng) and the 43 +/- 4% fall in sGaw following inhalation of LTE4 7.94 ng/GM (range 132-3701 ng). The LTE4 excretion rate increased significantly from 2.95 (range 0.6-17.5) ng.h-1 to 4.67 (range 0.8-20) ng.h-1 at 1.5 h following LTC4 inhalation; and from 1.8 (range 0.07-6.7) ng.h-1 to 6.9 (range 2.9-27.3) ng.h-1 at 1.5 h following LTE4 inhalation; and had returned from baseline by 3.5 h. There was a correlation between the dose of LTC4 inhaled and LTE4 excreted in the urine (r = 0.82 and r = 0.72, respectively). The % recovery of LTE4 in the urine, of the total dose of inhaled LTC4 or LTE4 administered, was 6.9 +/- 4.1% and 0.8 +/- 0.3%, respectively. Thus, inhalation of bronchoconstricting doses of LTC4 or LTE4 alter urinary LTE4 excretion in a dose-dependent fashion. This indicates that urinary LTE4 can be used as a marker of sulphidopeptide leukotriene synthesis in the lungs of patients with asthma.

Administration, Inhalation↗
PubMed1995

[Effect of endogenous and inhaled nitric oxide on pulmonary microcirculation].

The sites of action of endogenous and inhaled nitric oxide (NO) were reassured during hypoxic pulmonary vasoconstriction. Lungs of 21 adult cats were perfused in situ with autologous blood in zone-3 conditions. Capillary pressures were measured by the double-occlusion techniques and pressures in arterioles and venules 70-100 microns in diameter were measured by the servo-null micropuncture technique, both during normoxia (FiO2 = 0.3) and during hypoxia (FiO2 = 0.02). The effects of NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg), an inhibitor of NO synthase, and of inhaled NO (5-100 ppm) were also measured. The PO2 of the prefusate decreased from 187.6 +/- 5.3 mmHg during normoxia to 25.7 +/- 1.3 mmHg during hypoxia, and further decreased to 20.8 +/- 2.2 mmHg during hypoxia with 50 ppm NO (p < 0.05, compared with hypoxia only). Increases in pulmonary vascular pressure drop in response to hypoxia were 4.8 +/- 1.0 cmH2O and 9.1 +/- 1.4 cmH2O in non-treated and L-NAME-treated lungs, respectively (p < 0.05). L-NAME significantly increased hypoxic construction in the venous segment. The concentration of exhaled NO increased from 13 +/- 4 ppb during normoxia to 18 +/- 4 ppb during hypoxia (p < 0.1). Inhaled NO lowered not only pulmonary artery pressure but also capillary pressure in a dose-dependent manner, which reduced hypoxic pulmonary vasoconstriction. Pulmonary veins were more sensitive to inhaled NO than were arteries. Inhaled NO (50 ppm) dilated vessels smaller than 70 to 100 microns in diameter, by 39% (p < 0.05), and dilated venules greater than 100 microns in diameter by 26% (p < 0.05), but did not significantly dilate arterioles greater than 100 microns in diameter (11%). Inhaled NO did not significantly change the ratio of wet weight to dry weight. We conclude that both endogenous and inhaled NO attenuate hypoxic pulmonary vasoconstriction, with significant pulmonary venous dilation. The main site of action of inhaled NO is vessels smaller than 100 microns in diameter and venules greater than 100 microns in diameter. Inhaled NO (5-100 ppm) does not cause interstitial edema.

Administration, Inhalation↗
PubMed1996

[Use of inhaled bronchodilators by primary care patients].

OBJECTIVE: To find how widespread incorrect inhalation techniques are in patients on long-term inhalation treatments, comparing different methods and the health control standard. DESIGN: A descriptive crossover study. SETTING: Three Health Centres in Burgos. PATIENTS: People over 15 with at least a month on inhalation treatment. MEASUREMENTS AND MAIN RESULTS: A questionnaire was composed to find the characteristics of the patients and their illness. Then their inhalation method was qualified as correct, acceptable or incorrect, using a scale based on Newman's classic criteria. Average age was 63.8 +/- 15.6, with 66.5% men. 11.6% of patients were active smokers. The most common diagnosis was COPD (61.6%). 65% of the patients were monitored within primary care (PC). The most common inhalation method was pressurised aerosol (61%); 26.2% of patients used two or more different methods. Only 21.3% of patients correctly performed the technique of inhalation, with better results for patients under specialist care (SC) than PC. 10.5% of patients had never received instruction on an inhalation technique. The method with the best results was the dry dust one, with differences close to statistical significance. CONCLUSIONS: There is widespread incorrect use of methods of inhalation. Most people use a pressurised aerosol. There are a large number of patients who have never been shown the correct way to inhale.

Administration, Inhalation↗
PubMed1997

Use of inhaled corticosteroids in pediatric asthma.

Inhaled corticosteroids reduce asthma symptoms and exacerbations, improve lung function, and reduce airway inflammation and bronchial hyperreactivity more effectively than other treatments. However, inhaled corticosteroids may be unable to return lung function and bronchial hyperreactivity to normal when introduced for moderately severe asthma. This finding highlights the need to improve treatment strategy in pediatric asthma. The natural progression of persistent asthma may lead to loss of lung function and chronic bronchial hyperreactivity for children and adults. There is evidence to suggest that asthma acts via a chronic inflammatory process that causes remodeling of the airways with mucosal thickening and smooth muscle hypertrophy. An optimal treatment strategy would be one aimed at reducing the ongoing airway inflammation. Inhaled steroids ameliorate the inflammation, whereas this has not been documented for any other treatment. Delayed introduction of inhaled steroids appears to result in reduced improvement in lung function compared with the early use of inhaled steroids. This improved response from the earlier use of inhaled steroids appears to be valid at any stage of the disease. Therefore, a change in treatment strategy toward earlier introduction of corticosteroids may impede airway remodeling, bronchial hyperreactivity, and airway damage. No other treatment has been found to affect the course of the disease. Systemic side-effects, particularly inhibition of growth in asthmatic children using inhaled corticosteroids, do not seem to be cause for concern. Growth retardation has not been reported when inhaled corticosteroid doses of < or = 400 micrograms daily are individually tailored to each child's needs. The ongoing change in treatment strategy toward the earlier use of inhaled steroids in childhood asthma, as reflected in current revisions of various treatment strategies, therefore seems well founded.

Administration, Inhalation↗
PubMed1997

Efficacy and safety of inhalation therapy in chronic obstructive pulmonary disease and asthma.

The inhaled route has a number of well-recognized advantages over other routes for administration of drugs to the lungs. As the drug is delivered directly to its required site of action, only a small quantity is required for an adequate therapeutic response. Consequently, there is a low incidence of systemic side-effects compared with oral or intravenous administration. In addition, the onset of action of inhaled drugs is generally faster than that achieved by oral administration. Factors that can affect the quantity of inhaled particles reaching the lungs and their topographical distribution are manner of inhalation, aerosol characteristics and subject characteristics. The main types of inhaler device are metered-dose inhalers (MDIs), dry powder inhalers (DPIs) and nebulizers (jet and ultrasonic). There are advantages and disadvantages associated with all types of currently available inhaler device and there is still a clear need to develop more efficient devices that are easy to use. Respimat (Boehringer Ingelheim) is a novel soft mist inhaler that operates via a mechanism utilizing mechanical power rather than gas propellants, and represents an exciting development in this field.

Administration, Inhalation↗
PubMed1998

Effect of inhaled surfactant on pulmonary deposition and clearance of technetium-99m-DTPA radioaerosol.

UNLABELLED: To establish the effect of an aerosolized synthetic surfactant (Exosurf) on pulmonary 99mTc-diethylenetriamine pentaacetic acid (DTPA) aerosol deposition and clearance, radioaerosol studies were performed at varying times and under varying conditions after surfactant inhalation in canine lungs. METHODS: Twenty-three dogs had a baseline 99mTc-DTPA study; 2 days later the study was repeated after inhalation of a 1.5-ml/kg dose of Exosurf aerosolized by an ultrasonic nebulizer. The clearance half-time (T1/2) of 99mTc-DTPA from each lung was measured at different times (from 10 min to 3 hr) after Exosurf inhalation. For comparison, five animals had a 99mTc-DTPA study 10 min after inhalation of the same dose of saline as Exosurf. An additional five animals inhaled a 99mTc-DTPA-Exosurf mixture to investigate the distribution of Exosurf. RESULTS: Technetium-99m-DTPA distributed uniformly without significant changes in penetration indexes before and after inhalation of Exosurf and the 99mTc-DTPA-Exosurf mixture. After Exosurf inhalation, 99mTc-DTPA clearance at 10 min (T1/2; 35.6 +/- 8.7 min; n = 6) and 40 min (29.4 +/- 6.3 min; n = 4) was significantly prolonged compared with the matched baseline values (24.7 +/- 6.4 min, p < 0.0001; and 21.7 +/- 8.9 min, p = 0.01, respectively). However, later clearance times were not prolonged. By contrast, after saline inhalation, 99mTc-DTPA distributed inhomogeneously, and clearance times T1/2) were not altered from the matched baseline values. CONCLUSION: Aerosolized Exosurf distributes homogeneously in the lungs. Exosurf initially retards 99mTc-DTPA aerosol clearance, but 99mTc-DTPA transalveolar clearance returns to baseline rates within 1-2 hr. Technetium-99m-DTPA aerosol clearance measurements can be used to monitor the effect of inhaled Exosurf on pulmonary epithelial integrity.

Administration, Inhalation↗