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PubMed1998

Influence of flow rate on aerosol particle size distributions from pressurized and breath-actuated inhalers.

Particle size distribution of delivered aerosols and the total mass of drug delivered from the inhaler are important determinants of pulmonary deposition and response to inhalation therapy. Inhalation flow rate may vary between patients and from dose to dose. The Andersen Sampler (AS) cascade impactor operated at flow rates of 30 and 55 L/min and the Marple-Miller Impactor (MMI) operated at flow rates of 30, 55, and 80 L/min were used in this study to investigate the influence of airflow rate on the particle size distributions of inhalation products. Total mass of drug delivered from the inhaler, fine particle mass, fine particle fraction, percentage of nonrespirable particles, and amount of formulation retained within the inhaler were determined by ultraviolet spectrophotometry for several commercial bronchodilator products purchased in the marketplace, including a pressurized metered-dose inhaler (pMDI), breath-actuated pressurized inhaler (BAMDI), and three dry powder inhalers (DPIs), two containing salbutamol sulphate and the other containing terbutaline sulphate. Varying the flow rate through the cascade impactor produced no significant change in performance of the pressurized inhalers. Increasing the flow rate produced a greater mass of drug delivered and an increase in respirable particle mass and fraction from all DPIs tested.

Aerosols↗
PubMed1987

Diurnal rhythm of asthma.

A diurnal rhythm in the occurrence and severity of asthma symptoms is almost universal with disturbed sleep due to enhanced symptoms at night paralleled by a change in lung function. The mechanisms involved are not completely understood. However, it appears to be related to an exaggerated response to a circadian rhythm in lung function observed in healthy individuals. The circadian nature of asthma must be considered in diagnosis and evaluating the adequacy of therapy. Inhaled therapy with additional suppressive and anti-inflammatory treatment as required should be effective in treating most patients with nocturnal asthma.

Asthma↗
PubMed2003

[Differential lung ventilation by use of a combination of a laryngeal mask airway and an endotracheal tube in a pediatric patient with atelectasis of the right lung].

A 5-month-old boy was diagnosed as having complete atelectasis of the right lung due to RS virus infection at the age of 1 month. Conventional respiratory physical therapy, inhalation therapy and mechanical ventilation through an endotracheal tube failed to re-expand the right lung, while the left lung gradually became overinflated. We therefore tried differential lung ventilation by using a combination of a laryngeal mask airway and an extra long endotracheal tube (ID, 3.5 mm; length, 280 mm; Portex Pediatric Tracheal Tube, Extra length; SIMS Portex Co., Ltd. UK). Following induction of anesthesia, a laryngeal mask airway #2 was inserted. Then, an extra long endotracheal tube was inserted through the laryngeal mask airway and was guided to the right main bronchus with the aid of a fiberscope. The right lung was selectively lavaged and inflated with high pressure while ventilation was maintained through the laryngeal mask airway. The SpO2 value was maintained at more than 95% throughout the procedure despite some leakage from the ventilation system. The case demonstrates that differential lung ventilation by use of a combination of a laryngeal mask airway and extra long endotracheal tube is useful for the treatment of a pediatric patient with severe atelectasis.

Humans↗
PubMed1990

[Management of respiratory infection after open heart surgery].

The results of a retrospective study on the management of respiratory infection after open heart surgery in 370 consecutive cases are presented in this paper. The incidence of postoperative respiratory infection was 3.8% (14 cases). There was atelectasis of the lung in 3, pneumonia in 6 and acute suppurative bronchitis in 5 cases. Among the 6 patients with postoperative pneumonia, one died of sepsis and another died of consolidation of the lung. The remaining 12 attained uneventful recovery after reasonable treatment with antibiotics, expectorant, oxygen therapy, inhalation therapy, bronchial lavage and aspiration. The prevention measures of postoperative respiratory infection are also discussed.

Adolescent↗
PubMed2000

Bone mineral density in women with asthma on long-term inhaled corticosteroid therapy.

BACKGROUND: Inhaled corticosteroids (ICS) have become first line agents in the management of moderate-to-severe asthma. Long-term use of ICS is associated with decreased bone mineral density (BMD). OBJECTIVE: To investigate the prevalence of BMD loss and its severity in women with asthma on long-term ICS. METHODS: Fifty-six women with asthma on long-term ICS, attending an inner-city allergy clinic were selected to undergo bone densitometry in order to evaluate the association between BMD and the long-term use of ICS at different dose ranges. RESULTS: Women (60.7%) had decreased BMD either at the lumbar spine or hip region. Among postmenopausal women, 17.1% of those <65 years and 42.9% of those > or =65 years had osteoporosis compared with 5.7% (95% CI-3.9% to 8.5%) of those <65 and 29.3% (95% CI-25.7%-33.5%) of those > or =65 years reported in the NHANES III survey. The prevalence of low BMD increased as ICS dose increased from 5% in the low dose group to 50% in the high dose group (P < .002). There were significant linear trends of decline by dose in mean BMD for the hip (P < .001) and the lumbar spine (P < .002). Women who received medium or high doses of ICS had significantly greater bone loss than those receiving low doses. CONCLUSION: The findings of increasing BMD loss with increasing ICS dose reinforce the necessity to monitor BMD periodically in women on ICS, particularly in the high risk postmenopausal group and those on medium to high doses. There should be a concurrent continual attempt to lower the dose by supplemental nonsteroidal controller medications and providing nutritional and pharmacologic treatment of identified BMD loss in these patients.

Administration, Inhalation↗
PubMed1992

A comparison of bronchodilator therapy with or without inhaled corticosteroid therapy for obstructive airways disease. Dutch Chronic Non-Specific Lung Disease Study Group.

BACKGROUND: The morbidity from obstructive airways disease (asthma and chronic obstructive pulmonary disease) is considerable, and the mortality rate is rising in several countries. It has been hypothesized that long-term improvement in prognosis might result from vigorous bronchodilator or antiinflammatory therapy. METHODS: In a multicenter trial we compared three inhalation regimens in which a beta 2-agonist (terbutaline, 2000 micrograms daily) was combined with a corticosteroid (beclomethasone, 800 micrograms daily), an anticholinergic bronchodilator (ipratropium bromide, 160 micrograms daily), or placebo. Patients with airways hyperresponsiveness and obstruction who were 18 to 60 years old were followed for 2 1/2 years. RESULTS: Of the 274 patients enrolled, 56 percent had allergies. The mean forced expiratory volume in one second (FEV1) was 64 percent of the predicted value. The mean PC20 (the concentration of inhaled histamine causing a 20 percent decrease in FEV1, a measure of hyperresponsiveness) was 0.26 mg per milliliter. Withdrawal from the study, due mainly to pulmonary symptoms, was less frequent in the corticosteroid group (12 of 91 patients) than in the anticholinergic-drug group (45 of 92 patients) or the placebo group (44 of 91 patients; P < 0.001). The mean FEV1 (+/- SE) increased by 10.3 +/- 1.3 percent of the predicted value in the corticosteroid group within three months and remained stable thereafter, whereas it did not change in the other two groups (P < 0.001). The PC20 increased by 2.0 doubling concentrations in the corticosteroid group but did not change in the other groups (P < 0.001). In the corticosteroid group, patients who did not smoke, who had allergies, or who were less than 40 years old benefited more from their treatment than did those who smoked, did not have allergies, or were over 40, but all subgroups of the corticosteroid group had improvement as compared with the anticholinergic-drug or placebo group. CONCLUSIONS: The addition of an inhaled corticosteroid--but not an inhaled anticholinergic agent--to maintenance treatment with a beta 2-agonist (terbutaline) substantially reduced morbidity, hyperresponsiveness, and airways obstruction in patients with a spectrum of obstructive airways disease.

Administration, Inhalation↗
PubMed2003

Inhaled steroid therapy and hospitalization for bronchial asthma: trend in Tokushima University Hospital.

With the recognition that airway inflammation is present even in patients with mild bronchial asthma, therapy with inhaled corticosteroids is now indicated in various stages of patients. In the present article, we retrospectively examined the prescriptions for inhaled corticosteroids and other drugs for the treatment of outpatients with bronchial asthma at Tokushima University Hospital. We also analyzed asthma control in these patients, in terms of the incidence of emergency consultations and hospitalizations due to asthma exacerbations. To analyze the recent trend, the patients observed from 1998 to 2000 (recent years) were included, and for control purpose, those in 1990 and 1991 (earlier years) were also included. The percentage of patients treated with inhaled corticosteroids remarkably increased in recent years (mean; 81.3%) compared to earlier years (mean; 23.5%). In contrast, the usage of oral corticosteroids, oral xanthine derivatives, beta-adrenergic receptor agonists and anti-allergic agents tended to decrease in the 10 years period. After the introduction in 1995, considerable patients up to 25% have been treated with anti-leukotrienes. Emergency consultations decreased in recent years (mean; 0.18/patient/year) compared to earlier years (mean; 0.79/patient/year). Emergency hospitalizations also decreased in recent years (mean; 0.043/patient/year) compared to earlier years (mean; 0.23/patient/ year). In the present study, spread of inhaled corticosteroid therapy and decline in incidence of emergency consultation and hospitalization were simultaneously observed at Tokushima University Hospital, and the former has, at least in part, a contribution to the latter.

Administration, Inhalation↗
PubMed1980

Oesophagitis--a complication of inhaled steroid therapy.

The hazards of steroid therapy, both inhaled and oral, in the asthmatic patient are well recognized. The following case report presents an unusual complication of steroid therapy, namely, that of a concomitant Candida and Herpes simplex oesophagitis occurring in a steroid-dependent 15-year-old asthmatic who had been maintained on inhaled beclomethasone for approximately 15 monts. Oesophagoscopy revealed a 'cottage cheese' appearance of the distal oesophagus. Cultures of the biopsy specimens obtained during oesophagoscopy grew Candida and Herpes simplex virus. Lymphocyte stimulation studies were consistent with a primary cellular response, although the neutralizing antibody titres to the Herpes simplex virus were initially high and remained stable throughout the illness and convalescent period. The patient responded well to oral nystatin therapy and developed no evidence of disseminated herpes. Eleven months after the initial episode, the patient's oropharynx cultured Herpes simplex virus but not Candida. Doctors who care for asthmatic patients need to be aware of the possibility of a herpetic as well as a candidal oesophagitis as a significant complication of inhaled steroid therapy.

Administration, Intranasal↗
PubMed2003

Interferon therapy induces the improvement of lung function by inhaled corticosteroid therapy in asthmatic patients with chronic hepatitis C virus infection: a preliminary study.

STUDY OBJECTIVES: Several reports have suggested that subsets of asthmatic patients with chronic viral infection fail to respond to corticosteroid therapy. Therefore, this study was designed to determine that asthmatic patients with chronic hepatitis C virus (HCV) infection fail to improve lung function by inhaled corticosteroid therapy, and that interferon (IFN) therapy against HCV is effective for such patients. DESIGN: Prospective observational study. SETTING: University hospital. PATIENTS: Forty asthmatic patients with chronic HCV infection. INTERVENTIONS: After a 4-week run-in period, all asthmatic patients received therapy with inhaled beclomethasone dipropionate (BDP), 400 micro g twice daily for 6 weeks. After the first study, all asthmatic patients continued to receive inhaled BDP, and 30 HCV-positive asthmatic patients received IFN-alpha therapy for 6 months. MEASUREMENTS AND RESULTS: Prebronchodilator and postbronchodilator FEV(1) values were examined after a 4-week run-in period, after 6 weeks of BDP therapy, and at 1 year from the end of IFN therapy. After a 4-week run-in period as well as after 6 weeks of BDP therapy, there were no significant differences in either prebronchodilator or postbronchodilator FEV(1) values among the three groups. However, 1 year after the end of IFN therapy, the mean prebronchodilator and postbronchodilator FEV(1) values were significantly higher in the IFN responder group (n = 11) [prebronchodilator FEV(1), 1.93 L (SD, 0.13 L); postbronchodilator FEV(1), 2.28 L (SD, 0.15 L)] than in the IFN nontreatment group (n = 10) [prebronchodilator FEV(1), 1.78 L (SD, 0.10 L); p = 0.01; postbronchodilator FEV(1), 2.07 L (0.13 L); p = 0.005] or the IFN nonresponder groups (n = 19) [prebronchodilator FEV(1), 1.79 L (SD, 0.15 L); p = 0.006; postbronchodilator FEV(1), 2.07 L (SD, 0.18 L); p = 0.002]. Moreover, prebronchodilator and postbronchodilator FEV(1) values were significantly higher only in the IFN responder group at 1 year after the end of IFN therapy than after the 4-week run-in period (prebronchodilator FEV(1), p = 0.028; postbronchodilator FEV(1); p = 0.002) or after 6 weeks of BDP therapy (p = 0.016 and p = 0.004, respectively). CONCLUSIONS: Our findings suggest that chronic HCV infection in asthmatic patients is associated with impaired responses to inhaled BDP therapy and that intervention with IFN reverses such responses only in the IFN responder group.

Administration, Inhalation↗
PubMed1996

[Problems of inhaled steroid therapy in children with asthma].

Inhaled steroid therapy has become a most popular anti-inflammatory medication in asthmatic children. However, overreliance on inhaled steroids should not mislead the treatment of asthma because the best way to prevent asthmatic symptoms is the identification and control of triggers such as allergens and non-specific irritants. We should weigh the merits against adverse effects and make a correct decision to use inhaled steroids in each asthmatic child. Since the effectiveness of inhaled steroids mainly depends on the correct performance of inhalation therapy, we must educate patients and their family to develop a good partnership in asthma management as emphasized in every guideline.

Administration, Inhalation↗
PubMed1996

[Inhaled corticosteroid in out-patient management of asthma].

In 1988, we started to change our treatment policy, away from a polypharmaceutical approach including oral bronchodilators and oral anti-allergic agents available in Japan, toward an inhalation therapy including inhaled corticosteroids and inhaled beta-agonist. A marked decline in the number of asthma admission and death from asthma started coincidentally with the increased use of inhaled corticosteroid which were followed by the decreased use of inhaled beta-agonists and oral anti-asthma agents. The intensification of patient education mainly consisting of emphasizing on better understanding of benefits of inhalation therapy and a self-management is likely to play an important role in enhancing a protective effects of inhaled corticosteroids. Despite some limitations of inhaled corticosteroids, such as poorer dose response in elderly asthmatics and/or patients with severe disease, further introduction of guide-line treatment will result in a measurable improvement on asthma control.

Administration, Inhalation↗
PubMed2005

Bone ultrasonometric features and growth hormone secretion in asthmatic patients during chronic inhaled corticosteroid therapy.

BACKGROUND: Quantitative ultrasound bone densitometry (QUBD) is a new method to assess bone mineral density and bone microarchitecture. Corticosteroid (CS) therapy may diminish bone mass, alter bone quality and may influence growth hormone (GH) secretion and bone metabolism markers. Therefore, the aim of this study was to evaluate the effects of long-term therapy with inhaled CSs (ICSs) on structural bone characteristics and their correlations with GH secretion and bone markers in asthmatic patients. METHODS: In a cross-sectional study, we enrolled 60 adult patients with mild to moderate persistent asthma: 22 on chronic (>1 year) ICS therapy, 10 naive to ICSs treatment and 28 healthy control subjects. The groups were matched for age and BMI. Each subject underwent to QUBD at the phalanxes to assess bone microarchitecture by ultrasound bone profile index (UBPI), bone density by amplitude-dependent speed of sound (AdSos); test with GH-releasing hormone (GHRH) injection with calculation of peak GH and the Delta GH (peak GH-basal GH); and hormonal and bone markers measurements. RESULTS: Asthmatics treated with long-term ICS therapy showed a lower UBPI (P < 0.01) compared to controls (49.8 +/- 19.3 vs. 77.0 +/- 10.1, respectively) and to asthmatics never taking ICSs (73.2 +/- 9.6). In ICS-treated asthmatics, DeltaGH and GH-peak showed a significant correlation with UBPI. A significant difference was observed comparing asthmatics treated with ICSs to controls and asthmatics naive to ICSs in GH response to GHRH iv bolus. Serum osteocalcin was significantly reduced in asthmatic patients treated with ICSs. CONCLUSIONS: In asthmatic patients, long-term ICSs treatment produces negative effects on bone quality assessed by QUBD, and such effects are associated to an impaired GH secretion.

Administration, Inhalation↗
PubMed1998

Bone mineral density and body composition in patients with airflow obstruction--the role of inhaled steroid therapy, disease and lifestyle.

BACKGROUND: Inhaled steroid therapy has been shown to be associated with low bone mineral density (BMD) in asthmatic patients, but its effect in men has not been specifically studied; and the relative importance of therapy, disease and lifestyle leading to low BMD has not been investigated. OBJECTIVES: The study was designed to compare BMD in women and men who had airflow obstruction (asthma or COAD with or without inhaled steroid therapy) with normal controls. The role of inhaled steroid treatment, disease severity and lifestyle was studied among patients. METHODS: One hundred and fourty-four patients (106 on inhaled steroids and 38 not on inhaled steroids) and 212 age-matched controls were studied. Body composition and BMD (at the total body, hip and spine) were measured by dual-X-ray densitometry (DEXA). Forced expiratory volume (FEV1) was measured in patients. A validated questionnaire was administered to measure lifestyle factors. RESULTS: The body mass indices (BMI) (P < 0.001) and percentage of body fat (P < 0.001) were higher among female patients on inhaled steroids than controls. However, the BMD of the total body (P < 0.05) and spine (P < 0.001) were significantly lower in premenopausal and postmenopausal women than controls, respectively (P < 0.005). The BMD at the spine (P<0.01) and hip (P < 0.01) in male patients were significantly lower than the controls. By multiple regression, age and use of inhaled steroid was negatively associated with BMD at the hip (P < 0.01), but not at the spine (P>0.05). Cigarette smoking was associated with significantly lower BMD at the femoral neck (P < 0.05), and a low dietary calcium intake was associated with lower BMD at the spine (P<0.05). In women, use of inhaled steroid was not associated with significantly lower BMD. CONCLUSION: Men who had asthma and/or COAD had lower BMD, and this was not attributable entirely to steroid use. Cigarette smoking and a low dietary calcium intake may partially account for this difference. The difference in BMD between female patients and controls, even in those taking inhaled steroid, was small.

Absorptiometry, Photon↗
PubMed2001

Alendronate for the prevention of bone loss in patients on inhaled steroid therapy.

One hundred women on inhaled steroid therapy (dose range from 800 to <1600 microg per day) were randomized to receive 10 mg of oral alendronate or placebo (with 500 mg of calcium in the form of daily calcium carbonate). Bone mineral density (BMD) was measured at baseline, 6 months, and 12 months. The percentage changes in BMD were -0.80% in the placebo group and 2.99% in the alendronate group at the spine (p < 0.001 by analysis of covariance [ANCOVA]), and were -0.51% in the placebo group and 0.97% in the alendronate group at the femoral neck (p < 0.05 by ANCOVA). Five patients in the alendronate-treated group, and a similar number of patients in the placebo group, complained of mild gastric discomfort. We conclude that women on inhaled steroid therapy were at risk of accelerated bone loss, which could be prevented by a daily dose of 10 mg of alendronate.

Administration, Inhalation↗
PubMed1997

Osteoporotic vertebral fractures in a man under high-dose inhaled glucocorticoid therapy. A case-report with a review of the literature.

A 65-year-old man had surgery in June 1995 for femoral neuralgia. The plain films of the spine were normal at the time. In September of the same year, when he was beginning to walk gradually longer distances, he started experiencing back pain. Crush fractures of T8 and L2 were seen on plain films. His pain worsened, and he was admitted in December 1995. A third set of plain films disclosed fractures of all the vertebral bodies from T8 through L5, with increased density of the endplates of the same vertebras. Serum and urinary levels of calcium and phosphate were normal. Dual-energy X-ray absorptiometry demonstrated osteoporosis predominating in the trabecular bone. Evidence of increased bone resorption was seen on the histomorphometric study. Large amounts of dihydroxypyridinoline were found in the urine. Investigations for the classical causes of osteoporosis in males were unrewarding. Careful questioning revealed that the patient had been taking inhaled beclomethasone for seven years to treat chronic obstructive lung disease. Serum levels of cortisol and ACTH were low, consistent with a diagnosis of treatment-induced hypercorticism. To our knowledge, this is the first reported case of osteoporotic vertebral fractures in a male due to inhaled glucocorticoid therapy. Inhaled glucocorticoids are generally believed to induce only minimal systemic effects. However, decreased serum osteocalcin levels and increased urinary excretion of bone resorption markers have been reported in patients under inhaled beclomethasone therapy. Low spinal bone mineral density values correlated with the degree of pituitary-adrenal gland suppression as evaluated using the ACTH test have also been found in several groups of patients treated with inhaled glucocorticoids.

Administration, Inhalation↗