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PubMed1999

Recent developments in inhaled nitric oxide therapy of the newborn.

Inhaled nitric oxide therapy improves oxygenation and reduces the need for extracorporeal life support in near-term and term newborns with hypoxemic respiratory failure and persistent pulmonary hypertension of the newborn. Previous studies demonstrated that the efficacy of inhaled nitric oxide therapy is related to the underlying disease associated with persistent pulmonary hypertension and that lung recruitment strategies augment the response to this inhalational vasodilator. This review of recent studies evaluates new insight into important questions regarding the optimal dose of inhaled nitric oxide, potential adverse effects associated with inhaled nitric oxide therapy, and the potential role of inhaled nitric oxide in the premature newborn with hypoxemic respiratory failure.

Administration, Inhalation↗
PubMed1997

Postnatal follow-up of the oxygenation index, arterial to alveolar oxygen tension ratio and alveolar arterial oxygen tension difference values in neonates with the respiratory distress syndrome treated with conventional ventilatory support.

Recent development of sophisticated intensive care technique for use in newborn infants with the respiratory distress syndrome (RDS) has resulted in changes in the therapeutic strategies and moved the problem of neonatal survival into the realm of new therapeutic realities. At present, the mechanical ventilation methods form an integral part of the intensive care strategy of infants with RDS. They have come to the forefront of infant care because of their successful use in ventilatory support and children survival where other therapeutic modalities have failed. The present prospective observational longitudinal study was designed to assess the real-time convenience, reliability and accuracy of the changes in the oxygenation index (OI), arterial-to-alveolar oxygen tension ratio (a/A PO2) and alveolar-arterial oxygen gradient (A-a)DO2 in ventilator-dependent neonates with RDS, to analyze their feasibility and potential information yield in oxygen inhalation therapy as well as their prognostic implications and predictive value. Twenty neonates with RDS, heralded by respiratory failure which necessitated the initiation of oxygen inhalation therapy and ventilatory support within 24 hours of birth, were enrolled in the study. Ten of the infants survived and the remaining ten died. OI, (a/A PO2) and (A-a)DO2 were followed up sequentially and thoroughly analyzed as the primary outcome measures of the study. The indices were calculated on the basis of the complete monitoring of the ventilatory equipment parameters and acid-base status carried out on an hourly basis. Our results show that: 1. The combination of three indexes (OI, (a/A)PO2 and (A-a)DO2 we propose is a useful discriminating predictor of neonatal lung maturity reflecting arterial blood gas status in ventilator-dependent neonates with RDS. 2. The indices detect the efficacy of the modern conventional ventilatory support with real-time convenience and reliable accuracy forming the cornerstone of clinical decision-making in RDS neonatal intensive care and allowing timely corrections of the ventilatory equipment parameters. 3. The prospective follow-up of these indices improves the predictive value as compared to any single test of neonatal lung maturity and has important prognostic implications in the management of neonates with RDS.

Humans↗
PubMed1995

Effect of inhaled nedocromil sodium therapy on blood gas changes in children challenged with ultrasonically nebulized distilled water. A comparison of 8 mg versus 16 mg daily dose.

Changes in time course of blood partial pressures of oxygen (PtcO2) and carbon dioxide (PtcCO2) before, during and after challenge with ultrasonically nebulized distilled water (UNDW) were evaluated in 22 children with mild asthma in basal conditions, and after 8 weeks of therapy with inhaled nedocromil sodium at a daily dosage of 8 or 16 mg. PtcO2 and PtcCO2 were followed using transcutaneous O2 and CO2 monitoring system. All asthmatic subjects presented a significant decrease in PtcO2 and/or PtcCO2 (> 20% basal value) during or after challenge. After therapy, the decrease in PtcO2 and PtcCO2 was normalized in the group treated with 16 mg/day, whereas only a partial yet significant reduction in the decrease of O2 and CO2 was observed in the group assuming 8 mg/-day. These data indicate that inhaled nedocromil is effective in treating bronchial hyperresponsiveness in childhood and that the dose required to achieve this effect is of 16 mg/day.

Administration, Inhalation↗
PubMed1999

Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis.

OBJECTIVE: To appraise the data on systemic adverse effects of inhaled corticosteroids. METHODS: A computerized database search from January 1, 1966, through July 31, 1998, using MEDLINE, EMBASE, and BIDS and using appropriate indexed terms. Reports dealing with the systemic effects of inhaled corticosteroids on adrenal gland, growth, bone, skin, and eye, and reports on pharmacology and pharmacokinetics were reviewed where appropriate. Studies were included that contained evaluable data on systemic effects in healthy volunteers as well as in asthmatic children and adults. A statistical meta-analysis using regression was performed for parameters of adrenal suppression in 27 studies. RESULTS: Marked adrenal suppression occurs with high doses of inhaled corticosteroid above 1.5 mg/d (0.75 mg/d for fluticasone propionate), although there is a considerable degree of interindividual susceptibility. Meta-analysis showed significantly greater potency for dose-related adrenal suppression with fluticasone compared with beclomethasone dipropionate, budesonide, or triamcinolone acetonide, whereas prednisolone and fluticasone propionate were approximately equivalent on a 10:1-mg basis. Inhaled corticosteroids in doses above 1.5 mg/d (0.75 mg/d for fluticasone propionate) may be associated with a significant reduction in bone density, although the risk for osteoporosis may be obviated by post-menopausal estrogen replacement therapy. Although medium-term growth studies showed suppressive effects with 400-microg/d beclomethasone dipropionate, there was no evidence to support any significant effects on final adult height. Long-term, high-dose inhaled corticosteroid exposure increases the risk for posterior subcapsular cataracts, and, to a much lesser degree, the risk for ocular hypertension and glaucoma. Skin bruising is most likely to occur with high-dose exposure, which correlates with the degree of adrenal suppression. CONCLUSIONS: All inhaled corticosteroids exhibit dose-related systemic adverse effects, although these are less than with a comparable dose of oral corticosteroids. Metaanalysis shows that fluticasone propionate exhibits greater dose-related systemic bioactivity compared with other available inhaled corticosteroids, particularly at doses above 0.8 mg/d. The long-term systemic burden will be minimized by always trying to achieve the lowest possible maintenance dose that is associated with optimal asthmatic control and quality of life.

Administration, Inhalation↗
PubMed1994

The evolution of inhaler technology.

Historically, the evolution of inhalation therapy can be traced to India 4000 years ago. The antecedents of contemporary inhalation therapy, however, began in the nineteenth-century industrial age with the invention of the glass bulb nebulizer. From there, inhaler technology evolved along two pathways characterized by refinements in existent nebulizer technology and the invention of a portable inhalation device, the metered-dose inhaler (MDI). More recently, growing recognition of problems associated with MDI use (chiefly, its reliance on coordinated patient inhalation and actuation technique) led to modifications in the MDI itself with auxiliary devices (spacers) and the development of new inhaler systems--dry powdered inhalers (DPIs) and the breath-actuated metered-dose inhaler (BAI-MDI).

Asthma↗
PubMed2004

The ideal inhaler: design and characteristics to improve outcomes.

Inhalation therapy is Likely to continue to dominate asthma treatment. The pressurised metered dose inhaler (pMDI) accounts for most of the inhaler market world-wide, but is inefficient and difficult to use. Dry powder inhalers (DPIs) have several advantages over MDIs. They are breath-activated, easy and convenient to use and environmentally friendly. The Turbuhaler is the most widely used DPI, offering good deposition with sufficient inspiratory flow, but it provides no confirmation of dosing, exhibits high dose variation, has a high intrinsic resistance, and inspiratory flow profile-dependent drug deposition. The Novolizer (VIATRIS, Frankfurt, Germany) is a new DPI which has several characteristics of an 'ideal' inhaler. It is convenient and easy to use, demonstrate and teach, provides accurate and consistent drug delivery and provides patients with feedback of dose taken. The Novolizer is a promising new delivery system for inhalation therapy.

Anti-Asthmatic Agents↗
PubMed2006

Single-inhaler combination therapy for asthma: a review of cost effectiveness.

Clinical studies have shown that the combination of an inhaled corticosteroid (ICS) and a long-acting beta(2)-adrenoceptor agonist (LABA) for patients with asthma is more effective than the use of ICS alone in equivalent or higher doses, as well as the use of other combinations. However, the relatively higher acquisition costs for the combination therapy require assessment of the value of the incremental costs, especially from a societal perspective. This review provides an overall assessment of the cost effectiveness of ICS plus LABA combination therapy for asthma. A systematic literature research was conducted in MEDLINE to identify studies published between January 1994 and September 2005. Cost-effectiveness studies derived from 11 clinical studies were identified. The ICS plus LABA combination was compared with ICS alone in eight studies, ICS plus a leukotriene antagonist in two studies, and a leukotriene antagonist alone in one study. All studies focused on measuring direct medical costs in a total of six different healthcare systems, and three studies conducted sensitivity analyses, including productivity costs. Outcomes were measured in treatment success (changes in lung function), episode-free days, and symptom-free days by evaluating short-term follow-up. The combination of ICS and LABA was found to be more efficacious and cost effective compared with ICS alone or alternative combinations of controller medications. Further considerations for measuring long-term outcomes and dose-response relationships might be required to provide further evidence on the cost effectiveness of combination therapy with ICS plus LABA.

Acetates↗
PubMed2004

Tiotropium (Spiriva): a once-daily inhaled anticholinergic medication for chronic obstructive pulmonary disease.

Tiotropium represents a new generation of inhaled therapy. No other inhaled product has demonstrated effectiveness with once-daily dosing. Treatment has been associated with improved lung function, decrease in the number of exacerbations, increase in the time to first exacerbation, and improved quality of life. Adverse effects appear to be mild in nature, and the only significant adverse effect is dry mouth. Clinical trials show that tiotropium is more effective than placebo. When compared with current treatment for chronic obstructive pulmonary disease, tiotropium is at least as effective as salmeterol and more effective than ipratropium; moreover, the once-a-day dosing increases the likelihood of patient compliance. The guidelines of the Global Initiative for Chronic Obstructive Lung Disease recommend bronchodilator medications as first-line therapy in the symptomatic management of chronic obstructive pulmonary disease. Tiotropium, an anticholinergic bronchodilator, should be considered a first-line agent for patients with chronic obstructive pulmonary disease.

Journal Article↗
PubMed1997

Aerosol therapy in the equine species.

Inhalation therapy plays an increasing role in the management of equine respiratory disorders. This alternative to systematic treatment permits a high concentration of medication to act locally while minimizing side effects and residues. In human medicine, literature in this field is prolific and continuously renewed, whereas in veterinary medicine, applications of aerosol therapy are less extensive. This review considers the principles of action of the different types of devices used for inhalation, i.e., nebulization, metered-dose inhalation and dry powder inhalation, describes the technical and practical requirements for their use in the equine species and considers the advantages and disadvantages of each inhalation device. The pharmacological agents currently administered to horses by inhalation are also discussed. Perspectives of aerosol therapy in the equine species, including aerosols already used in human medicine and their potential applications for horses are described.

Adrenal Cortex Hormones↗
PubMed2006

A brief history of inhaled asthma therapy over the last fifty years.

This year is the 50th anniversary of the introduction into clinical use of the first modern inhaler for the management of asthma--the pressurised metered-dose inhaler (pMDI). The pMDI was initially used for the administration of the non-selective beta-agonists adrenaline and isoprenaline. However, the epidemic of asthma deaths which occurred in the 1960s led to these drugs being superseded by the selective short-acting beta-agonist salbutamol, and the first inhaled corticosteroid (ICS) beclomethasone. At the same time, sodium cromoglycate was introduced, to be administered via the first dry-powder inhaler--the Spinhaler--but owing to its relatively weak anti-inflammatory action its use is now very limited. Over the last 10 years, the long-acting beta-agonists (LABAs) have become an important add-on therapy for the management of asthma, and they are now often used with ICS in a single ICS/LABA combination inhaler.

Administration, Inhalation↗
PubMed1996

Drugs by inhalatory route: an overview and upcoming clinical perspectives.

The physical properties of aerosols are reviewed. The physiological basis of inhalation therapy is then briefly reviewed together with the aerosol devices currently available and the therapeutic uses of inhaled drugs, focusing on the treatment of parenchymal lung diseases and extra respiratory disorders. Finally, new perspectives for inhalation therapy are examined.

Administration, Inhalation↗
PubMed2006

Diagnosing and managing infection in CF.

Acute and chronic bacterial infections of the lower respiratory tract remain one of the hallmarks of cystic fibrosis lung disease. We here review some of the controversial areas of diagnosing airway infection in CF patients including the use of techniques such as induced sputum and bronchoalveolar lavage. Treatment strategies have evolved over the years and there is ongoing discussion as to whether to treat on the basis of symptoms, positive cultures alone or continuously regardless of clinical and laboratory findings. Prophylactic antibiotic therapy with anti-staphylococcal antibiotics has been linked to a higher incidence of P. aeruginosa infection, but it is still unclear whether this side effect is limited to broader spectrum antibiotics such as cephalosporins. Early antibiotic therapy against P. aeruginosa has become an accepted treatment strategy as it not only delays the onset of chronic infection, but also leads to eradication of the organism in the majority of patients. So far no evidence exists that combination therapy is superior to inhaled therapy alone. In addition, the optimal duration of therapy type of inhaled antibiotic as well as the optimal dose has not been clarified. Studies are currently ongoing to resolve these issues.

Anti-Bacterial Agents↗