Acute adrenal insufficiency after discontinuation of inhaled corticosteroid therapy.
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Acute Disease↗
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Inhaled steroid therapy in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) remains difficult to manage. Patients with COPD present with progressive dyspnea; difficulty in stopping smoking; recurrent exacerbations; and, ultimately, respiratory failure. Because of the lack of proven treatments for COPD and because inhaled corticosteroids can prevent airway inflammation and permanent lung damage in patients with asthma, it has become common practice to prescribe inhaled corticosteroids for patients with COPD despite a lack of data suggesting that these agents have any long-term benefit in these patients. In the past 12 months, three randomized, double-blind, placebo-controlled clinical trials (the European Respiratory Society Study on Chronic Obstructive Pulmonary Disease, the Copenhagen City Lung Study, and the Inhaled Steroids in Obstructive Lung Disease study) designed to assess the long-term effect of inhaled corticosteroids in patients with varying severity of airway obstruction have been presented. The results of these studies have been disappointing; they show little to suggest that any long-term benefit is gained from using inhaled corticosteroids in most patients with COPD, whether they continue to smoke or not.
Administration, Inhalation↗
[Long-term therapy with inhalation of dexamethasone ester aerosol].
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Adrenal Cortex Hormones↗
Advances in asthma and COPD treatment: combination therapy with inhaled corticosteroids and long-acting beta 2-agonists.
Asthma treatment guidelines advocate the use of long-acting beta2-agonists (LABA) in addition to inhaled corticosteroids (ICS) in patients whose asthma is uncontrolled by ICS alone, thereby addressing two processes fundamental to asthma: bronchoconstriction and inflammation. Superior control--including a reduction in severe exacerbations--of asthma and COPD by ICS/LABA combination therapy has been demonstrated. Results from clinical studies suggest additive and potentially synergistic effects when the two agents are used in combination. No new safety-related issues have been identified with ICS/LABA compared with the monocomponents. The exact mechanisms for the enhanced efficacy of ICS/LABA combinations are under investigation but likely include drug interactions at the receptor level and interwoven signalling pathways, which may result in improved function of 2- adrenoceptors and steroid receptors. Data from preclinical studies provide evidence of additive, compensatory, complementary and synergistic effects of ICS and LABA in the control of inflammation and airway and lung remodelling. These effects may contribute to the improved efficacy seen when treating asthma and COPD with ICS/LABA combinations in clinical studies. Two ICS/LABA combination products are available: budesonide/formoterol (Symbicort) and salmeterol/fluticasone propionate (SeretideTM). An ICS/LABA combination in a single inhaler represent safe, effective and convenient treatment options for the management of patients with asthma and COPD. Clinical results also suggest that adjustable dosing with budesonide/formoterol provides better asthma control than fixed dosing. Further elucidation of the underlying mechanisms responsible for this superior disease control is needed.
Adrenal Cortex Hormones↗
[Pentamidine inhalation for therapy and prophylaxis of Pneumocystis carinii pneumonia. Results of the working discussion of the Section for Antiparasite Chemotherapy of the Paul Ehrlich Society].
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Acquired Immunodeficiency Syndrome↗
Serum interleukin-5 levels are elevated in mild and moderate persistent asthma irrespective of regular inhaled glucocorticoid therapy.
BACKGROUND: Interleukin-5 (IL-5) is thought to play a pivotal role in the pathogenesis of asthma. High levels of circulating IL-5 have been documented in acute asthma. However, serum IL-5 levels in mild to moderate asthmatics and the influence of regular use of inhaled glucocorticoids, is not known. METHODS: Fifty-six asthmatics and 56 age and sex matched controls were recruited prospectively from an outpatient department. Information on asthma severity and treatment was gathered by a questionnaire. Serum IL-5, total IgE and specific IgE levels were measured in a blinded fashion. RESULTS: There were 32 atopic and 24 non-atopic mild-to-moderate asthmatics. The median serum IL-5 levels in atopic asthmatics (9.5 pg/ml) and in non-atopic asthmatics (8.1 pg/ml) were significantly higher than in normal controls (4.4 pg/ml, both p < 0.003). However, median serum IL-5 levels in atopic and non-atopic asthmatics were not significantly different. The median serum IL-5 level was insignificantly higher in fourteen moderate persistent asthmatics (10.6 pg/ml) compared to forty-two mild persistent asthmatics (7.3 pg/ml) (p = 0.13). The median serum IL-5 levels in asthmatics using regular inhaled steroids (7.8 pg/ml) was not significantly different from those not using inhaled steroids (10.2 pg/ml). Furthermore, serum total IgE levels and eosinophil counts were not significantly different in those using versus those not using inhaled glucocorticoids. CONCLUSION: Serum IL-5 levels are elevated in mild and moderate persistent atopic and non-atopic asthmatics. Regular use of inhaled glucocorticoids may not abrogate the systemic Th2 type of inflammatory response in mild-moderate persistent asthma.
Journal Article↗
The acute asthmatic patient in the ED: to admit or discharge.
Treating asthma in the emergency department (ED) always involves the potentially difficult decision as to whether to discharge the patient, to continue treatment, or to admit to the hospital. The following are useful guidelines. (1) The duration of the bronchospasm, frequency of visits, history of previous endotracheal intubation, pulse rate, and accessory muscle use are findings affecting successful discharge from the ED. (2) Patients with peak expiratory flow rate (PEFR) of < 20% and who do not respond to inhalant therapy, with PEFR values persisting at < 40% of predicted, will require 4 or more days to resolve and should be admitted to the hospital. (3) Patients with a PEFR between 40% and 70% of predicted after initial inhalant therapy may well be responsive to steroids in the ED, but an ED will adequately need to care for the patient for 5 to 12 hours while waiting for the onset of action of glucocorticoids. Discharged with glucocorticoids, this group has a 6% relapse rate within 10 days of the ED visit. (4) Patients with a PEFR of > or = 70% have a 14% relapse rate after discharge without glucocorticoids. Other reasons to consider admission are pneumonia, barotrauma, lability, prominent psychiatric difficulties, poor access to medications, poor educability, fear of steroids, patients on glucocorticoids or those who have recently stopped glucocorticoids, and evening discharges of patients from the ED, which all predispose to relapses of acute asthma. To decrease the relapse rate, provocative factors should be reviewed with the patient, as well as access to medication and use of spacers, inhaler techniques, PEFR meters, self-management plans, and referral to a defined appointment at 24 to 48 hours of the ED visit.
Acute Disease↗
Intravenous use of glycopyrrolate in acute respiratory distress due to bronchospastic pulmonary disease.
A patient with acute respiratory distress secondary to emphysema and reactive airway disease had inadequate tidal volumes with and without endotracheal intubation. Because of the patient's failure to respond to maximal standard bronchodilator therapy and the physical inability to ventilate the patient by manual positive pressure, he received IV glycopyrrolate (0.2 mg) approximately 50 minutes after admission to the ED. The patient's condition immediately improved, as evidenced by the ability to manually ventilate the patient; he developed increased tidal volumes; and he began responding to inhalation therapy. This is the first reported case of IV glycopyrrolate administration for chronic obstructive pulmonary disease or asthma in the literature and demonstrates an instance in which inhalation therapy was ineffective due to low tidal volumes.
Acute Disease↗
Combined therapy with inhaled nitric oxide and intravenous prostacyclin in an infant with alveolar-capillary dysplasia.
Severe persistent pulmonary hypertension of the newborn (PPHN) remains a significant cause of neonatal morbidity and mortality with limited effective treatment options. We present the first case of a neonate with PPHN treated concurrently with inhaled nitric oxide (iNO) and intravenous prostacyclin (PGI2). He ultimately was diagnosed with alveolar-capillary dysplasia, a rare and fatal cause of pulmonary hypertension. However, his partial response to treatment demonstrates a possible role for combined therapy with iNO and PGI2 in infants with severe PPHN.
Antihypertensive Agents↗
Current status and future prospects for new therapies for pulmonary tuberculosis.
PURPOSE OF REVIEW: Nowadays tuberculosis is becoming a worldwide problem, and according to the World Health Organization, which declared tuberculosis a global health emergency in 1993, each year 8 million people worldwide develop the active disease and almost 3 million die. RECENT FINDINGS: Due to this problem there is an urgent need for new strategies and drugs to fight against this disease. In this context, this review describes promising new classes of compounds against tuberculosis that are under study, as well as promising drugs that may soon be introduced onto the market. Another subject reported in this review is inhaled therapy, an important route under study for delivering antitubercular drugs directly to the lungs. SUMMARY: The implications of new drugs and inhaled therapy in tuberculosis treatment are fewer toxic side-effects, improved pharmacokinetics properties, extensive and potent activity against Gram-positive and Gram-negative bacteria, including resistant strains, and a reduction in the total treatment time.
Antitubercular Agents↗
Combined surfactant therapy and inhaled nitric oxide in rabbits with oleic acid-induced acute respiratory distress syndrome.
Intratracheal administration of surfactant and inhaled nitric oxide (INO) have had variable effects in clinical trials on patients with acute respiratory distress syndrome (ARDS). We hypothesized that combined treatment with exogenous surfactant and INO may have effects in experimental ARDS. After intravenous infusion of oleic acid in adult rabbits and 4-6 h of ventilation, there was more than a 40% reduction in both dynamic compliance (Cdyn) of the respiratory system and functional residual capacity (FRC), a 50% increment of respiratory resistance (Rrs), a 70% reduction in PaO2 /FIO2, and an increase in intrapulmonary shunting (Q S/Q T) from 4.4 to 33.5%. The animals were then allocated to groups receiving (1) neither surfactant nor INO (control), (2) 100 mg/kg of surfactant (S) administered intratracheally, (3) 20 ppm INO (NO), or (4) 100 mg/kg of surfactant and 20 ppm INO (SNO), and subsequently ventilated for 6 h. After the period of ventilation, the animal lungs were used for analysis of disaturated phosphatidylcholine (DSPC) and total proteins (TP) in bronchoalveolar lavage fluid (BALF), and for determination of alveolar volume density (VV). The animals in the control group had the lowest survival rate, and no improvement in lung mechanics and blood oxygenation, whereas those in the S group had a modest but statistically significant improvement in Cdyn, Rrs, PaO2 and FRC, reduced Q S/Q T, lowered minimum surface tension (gammamin) of BALF, and increased DSPC/ TP and alveolar VV. The NO group had increased PaO2 and reduced Q S/Q T. The SNO group showed improved Cdyn, Rrs, FRC, DSPC/TP, alveolar VV, and gammamin of BALF comparable to the S group, but there was a further increase in survival rate and PaO2, and additional reduction in Q S/Q T and TP in BALF. These results indicate that, in this animal model of ARDS, a combination of surfactant therapy and INO is more effective than either treatment alone.
Administration, Inhalation↗
Knowledge, attitudes, and practices of parents of asthmatic children in Cape Town.
To obtain information useful to asthma care in a relatively poor, high asthma prevalence population, a focus group study was undertaken with 72 parents of children with asthma or recurrent wheezing. There was a reasonable level of understanding of the causes of asthma, although variable acceptance of the diagnosis. Willingness to undertake home management of acute episodes and environmental control measures was high. Reported treatment was characterized by reliance on syrups, use of home remedies, resistance to inhaled therapy, and relatively low compliance with prescribed treatment. There was agreement on the poor level of service offered by doctors and public sector clinics. Asthma education in this population needs to build on what parents know and accept, but stress the relative safety of inhaled therapy, the need for maintenance therapy, and the value of pre-exercise prophylaxis, house dust mite control, and smoking cessation. There is an urgent need to improve the quality of asthma care provided by public sector clinics.
Adult↗
Combination therapy with inhaled long-acting beta2-agonists and inhaled corticosteroids: a paradigm shift in asthma management.
Long-acting inhaled beta2-agonists and inhaled corticosteroids are classes of drugs with different mechanisms of action that are commonly used to provide effective long-term control of persistent asthma. Scientific and clinical data support the complementary mechanisms of action of the inhaled corticosteroids and the long-acting beta2-agonists in achieving a superior level of asthma control. In addition, evidence supports significant reductions in exacerbations and effective control of airway inflammation with an inhaled corticosteroid and a long-acting beta2-agonist versus higher dosages of inhaled corticosteroids or combinations of other therapeutic agents with an inhaled corticosteroid. Finally, there are distinct economic advantages to combining an inhaled corticosteroid and a long-acting beta2-agonist in the treatment of asthma relative to other treatment regimens.
Administration, Inhalation↗
Current issues for establishing inhaled corticosteroids as the antiinflammatory agents of choice in asthma.
Airway inflammation appears to be present even in the mildest of asthma, and inhaled corticosteroids now form the mainstay of asthma therapy. Inhaled corticosteroids largely avoid the adverse effects associated with oral steroids and are now recommended in newly detected disease. Inhaled corticosteroids reduce airway inflammation, airway hyperresponsiveness, and the symptoms of asthma and improve lung function, irrespective of the patient's age or asthma severity. Several different inhaled corticosteroids are available as therapeutic options for the treatment of asthma, and these include fluticasone propionate, beclomethasone dipropionate, and budesonide. The efficacy and safety of inhaled corticosteroids are compared in this article, and inhaled corticosteroid therapy is also compared with other therapies. Recently, there has been a consensus that the optimal use of inhaled corticosteroids for asthma management is using a "start high--go low" approach, and the reasons for this are discussed.
Administration, Inhalation↗
Evaluating the effects of "triple therapy" with inhaled corticosteroids, long-acting beta2-agonists, and leukotriene modifiers in asthma.
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Acetates↗
Long-acting beta2-agonists or leukotriene receptor antagonists as add-on therapy to inhaled corticosteroids for the treatment of persistent asthma.
It is well accepted that the combination of inhaled corticosteroids (ICSs) and long-acting beta2-agonists (LABAs) is effective in achieving asthma control, as it treats both components of asthma pathophysiology, namely inflammation and smooth muscle dysfunction of the airways. Leukotriene receptor antagonists (LTRAs) can also be used as add-ons to ICS therapy in patients whose asthma is not controlled by ICSs alone. The purpose of this review is to compare the effectiveness of ICSs plus LABAs with that of ICSs plus LTRAs for the treatment of persistent asthma that is not controlled by ICSs alone. Several studies have shown that, in comparison with an ICS plus an LTRA, the addition of an LABA to ICS therapy provides greater improvements in pulmonary function and overall control of asthma as measured by use of rescue medication and the number of exacerbations of the asthma, symptom-free days and symptom-free nights. The greater improvements in pulmonary function observed with an ICS plus the LABA, salmeterol, occurred within the first week of treatment (at first treatment assessment), and remained significantly greater than those achieved with an ICS plus an LTRA over the duration of the treatment. Moreover, the salmeterol-fluticasone propionate combination (SFC) produces consistently greater improvements in pulmonary lung function and control of asthma than does the addition of an LTRA to fluticasone propionate. In addition, SFC is a more cost-effective treatment option than fluticasone propionate plus montelukast for patients with asthma that is uncontrolled by ICSs alone. Important cost savings can be made with SFC in clinical practice compared with other combinations of ICSs plus salmeterol or ICSs plus LTRAs.
Adrenergic beta-2 Receptor Agonists↗
Long-acting inhaled anticholinergic therapy improves sleeping oxygen saturation in COPD.
Oxygen desaturation occurs during sleep in severe chronic obstructive pulmonary disease (COPD), especially during rapid eye movement (REM) sleep, due to hypoventilation and ventilation-perfusion mismatching, but the possible contribution of airflow limitation is unclear. In a randomised, placebo-controlled, double-blind study of severe, stable COPD patients, the authors compared 4 weeks treatment with a long-acting inhaled anticholinergic agent (tiotropium), taken in the morning (tiotropium-AM), or in the evening (tiotropium-PM), on sleeping arterial oxygen saturation (Sa,O2) and sleep quality. Overnight polysomnography was performed at baseline and after 4 weeks treatment. A total of 95 patients with awake resting arterial oxygen tension < or = 9.98 kPa (75 mmHg) were randomised, with a mean age of 66.4 yrs and mean forced expiratory volume in one second (FEV1) of 32% predicted. A total of 80 patients completed the study, of which 56 fulfilled the polysomnographic criterion of at least 2 h sleep in both sleep study nights and represent the group analysed. Tiotropium significantly improved spirometry compared with placebo. Both tiotropium-AM and tiotropium-PM groups had higher Sa,O2 during REM than placebo (+2.41% and +2.42%, respectively, and both pooled and tiotropium-PM groups had higher Sa,O2 during total sleep time (+2.49% and +3.06%, respectively). End-of-treatment FEV1 correlated with Sa,O2 during REM sleep, however, tiotropium did not change sleep quality. Sustained anticholinergic blockade improves sleeping arterial oxygen saturation without affecting sleep quality.
Administration, Inhalation↗
Changes in asthmatic patients' symptoms and lifestyles on institution of inhaled budesonide therapy.
An open, multi-centre, general practice study was carried out in 1661 asthmatic patients to assess the efficacy, in terms of symptom relief and changes in lifestyle, of budesonide and to record objective lung function changes and any adverse events. After a 1-week run-in period on any pre-trial anti-asthma medication, patients received either 200 micrograms or 400 micrograms budesonide twice daily by metered dose inhaler for 4 weeks. Peak expiratory flow rate (PEFR) was measured by the doctor on entry, after the run-in, and at the end of the study and patients were asked to complete diary cards on a daily basis to record compliance, bronchodilator usage and the severity of cough, wheeze and sleep disturbance, and weekly to record 5 lifestyle assessments, e.g. physical activity. Analysis of data from the clinic visits and 1375 completed diary cards showed that PEFR increased significantly from 321 +/- 3 l/min at the end of the run-in to 368 +/- 3 l/min at the end of the trial; 77% of patients had an improved PEFR. Bronchodilator use decreased significantly from 4.2 +/- 0.1 times/day during the run-in period to 3.0 +/- 0.1 times/day at the end of the study; 65% of patients used less bronchodilator. Significant improvements were recorded in all the symptoms and lifestyle indices monitored; 76% of patients improved in at least 5 of the 11 assessments. Treatment-emergent adverse events occurred in 103 (6%) of patients: none was classified as serious or unexpected. No sub-group of patients was identified in which the results were at variance from the full sample. It is concluded that budesonide improves patients' lifestyle and ability to carry out normal activities, as well as improving PEFR and reducing bronchodilator use, in mild to moderately severe asthmatics treated in general practice.
Administration, Inhalation↗