Stepping-down inhaled corticosteroid therapy in stable asthma: a secondary care perspective.
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Administration, Inhalation↗
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A pilot study of aerosolized N-acetylcysteine for idiopathic pulmonary fibrosis.
OBJECTIVE: Idiopathic pulmonary fibrosis poses a significant therapeutic challenge because of its progressive course. Since oxidative stress plays an important role in the pathogenesis of idiopathic pulmonary fibrosis, an open, randomized trial of long-term inhalation therapy with the antioxidant, N-acetylcysteine was conducted. METHODOLOGY: A total of 30 patients with idiopathic pulmonary fibrosis were randomly assigned to one of the following inhalation therapies: N-acetylcysteine (352 mg per day) or bromhexine hydrochloride (4 mg per day) as the control. Efficacy was assessed by analysing changes occurring from baseline to 12 months in pulmonary function, the 6-min walking test, high-resolution CT, health-related quality of life, and serum KL-6-values. RESULTS: Four patients (n=2 in each group) died within 12 months due to progression of idiopathic pulmonary fibrosis. A total of 22 patients (control, n=12; N-acetylcysteine, n=10) completed the study. At 12 months there were significant differences between the N-acetylcysteine and control groups in terms of mean changes in lowest SaO(2) during the 6-min walking test (-0.3+/- 2.1% vs -6.8+/-1.8%, P<0.05), serum KL--6 (-482+/-220 U/mL vs 176+/-204 U/mL, P<0.05), and the ground-glass score on high-resolution CT (-1.3+/-1.6 vs 6.7+/-1.5, P<0.01). No significant differences were observed in pulmonary function, 6-min walking distance or quality of life. CONCLUSIONS: These data suggest that although long-term aerosolized N-acetylcysteine administration did not influence pulmonary function or quality of life, it may delay disease progression as evidenced by exercise desaturation, high-resolution CT, and serum KL-6.
Acetylcysteine↗
Inhaled budesonide therapy for patients with stable COPD.
A significant minority of patients with COPD have favorable response to corticosteroid treatment. In addition, the benefit of corticosteroid treatment may be outweighed by the side effects. Long-term administration of inhaled steroids is a safe means of treatment. We hypothesized that treatment with high-dose inhaled budesonide would improve clinical symptoms and pulmonary function in subjects with COPD, and that the response to inhaled beta 2-agonist will serve to individualize steroid responders. We compared a 6-week course of 800 micrograms/d inhaled budesonide with placebo, separated by 4 weeks when no medication was taken, in a double-blind crossover trial, in 8 patients responding to inhaled beta 2-agonist, and in 22 nonresponders with stable COPD. In six of eight "responders to beta 2-agonist," there was a significant improvement in the FEV1 (defined as > or = 20%) following inhaled budesonide, as compared with placebo. In the 22 "nonresponders to beta 2-agonist," there was no significant improvement in the mean FEV1 (1.41 +/- 0.1 L before, and 1.61 +/- 0.1 L after treatment) with inhaled budesonide or placebo. Over the 6-week course of treatment by either budesonide or placebo, the nonresponders reported similar beta 2-agonist consumption (4.8 +/- 0.2 and 5.0 +/- 0.1 puffs per patient per day, respectively). However, there was a significant difference between the two periods of treatment in the responders as for the mean daily number of beta 2-agonist inhalations (2.4 +/- 0.1 in the budesonide period as compared with 5.3 +/- 0.1 in the placebo period; p < 0.005). We conclude that treatment with inhaled steroids improved spirometry data and inhaled beta 2-agonist consumption in about 25% of patients with stable COPD, and this rate is increased to about 75% in patients who respond to beta 2-agonist inhalation.
Administration, Inhalation↗
Nitrogen dioxide production in a nitric oxide inhalation system using the Servo Ventilator 900C.
During nitric oxide (NO) inhalation therapy, toxicity may be produced by the reactive metabolite nitrogen dioxide (NO2). The purpose of the present study was to determine the NO2 concentration in a NO inhalation system used for respiratory failure in children at relatively low concentrations of NO (< 20 ppm). The production of NO2 in the NO inhalation system using the Servo Ventilator 900C connected to the test lung under each of 30 combinations of NO concentrations (0, 4, 8, 12, 16, and 19 ppm) and inspired oxygen (O2) concentrations (21, 40, 60, 80, and 100%). Pressure controlled ventilation was used with a respiratory rate of 20 breaths/min. NO and NO2 measurements were obtained on the inspiratory side of the Y-piece connected to the test lung. At a given NO level, increases in the concentration of inspired O2 resulted in increases in the concentration of NO2 produced, as did increases in the amount of NO at a given concentration of O2. The mean NO concentration at the inspiratory site of the Y-piece did not exceed 0.05 ppm (the limit of NO2 as an outdoor air pollutant in the United States) when the NO concentration did not exceed 8 ppm, regardless of the O2 concentration. NO inhalation therapy for children with severe respiratory failure using the Servo Ventilator 900C can be performed safely when the concentration of NO does not exceed 8 ppm.
Nitric Oxide↗
Knowledge versus practice: the necessity of education for successful guideline implementation.
This study assessed physicians' familiarity with a practice guideline for bronchiolitis, evaluated attitudes regarding guidelines, determined preference of educational materials for guideline accessibility and examined the relationship between guideline familiarity and attitudes with clinical practice behaviors. Six months following guideline implementation, surveys were distributed to eligible physicians. The response rate was 68%. Retrospective analyses of inhalation therapies across three study cohorts were also performed. Most physicians surveyed in this study were aware of and utilized a recently introduced guideline, though use of unproven inhalation therapies continued. Despite demonstrated efficiencies of care, continued educational intervention is necessary to sustain these gains.
Arkansas↗
[Exposure of relatives of patients after stationary radioiodine therapy by inhalation of 131I in their homes].
AIM: From a model of iodine metabolism exhalation coefficients shall become derived to calculate 131I exhalation by patients after a radioiodine treatment. The validity of these exhalation coefficients shall be reviewed by whole body activity measurements of relatives of patients, who inhaled the radioiodine exhaled by the patients in their homes. The exposure of relatives to patients of a nuclear medical ward after release by exhalation of iodine-131 is investigated. METHODS: Iodine 131I-activity of 17 relatives to patients who had to undergo a radioiodine therapy became measured in a whole body counter only a few days after release of the patient from the nuclear medical ward. The results of the measurements have been compared with the results of calculations according to the model of iodine metabolism. RESULTS: The calculated values of incorporated radioiodine in the relatives of the patient at time of measurement (Amodel) correlate with the measured whole body activity (AGK) according to the regression: Amodel = AGK -47.3 (r2 = 0.959). This relation holds if 2.1 micrograms of iodine become exhaled per day of the 60 micrograms of iodine which are the daily intake of iodine by food. The exposure of all relatives did never exceed 100 microSveff. Using the same model parameters the effective dose equivalent of the relatives to our patients rises up to 6.5 mSv under ambulant radio therapy condition. CONCLUSION: The daily exhalation of 131I is able to be calculated by a mathematical model of iodine metabolism. After staying of patients at least 3 days in a nuclearmedical ward the exposure of relatives of patients in their home does not exceed the value of 100 microSveff by inhalation of iodine-131. This are 10% of the limit of 1 mSveff according to the Recommendations of the Commission on Radiological Protection (ICRP 60). Radioiodine therapy outside of a hospital and "iodine therapy tourisme" of German patients to other countries cannot be accepted.
Air Pollution, Indoor↗
Drug delivery in asthma: a comparison of spacers with a jet nebuliser.
BACKGROUND: Although spacer devices are frequently used for aerosol therapy in asthma, the commonly used spacers have undergone little controlled evaluation, and their relation to nebuliser therapy is unclear. AIMS: The aims of this study were to compare three delivery methods (Breath-A-Tech spacer, Volumatic spacer and jet nebuliser) for the administration of salbutamol to reverse acute histamine induced airway narrowing in asthma (Study 1); and to assess asthma control during two weeks use of inhaled therapy via Volumatic or Breath-A-Tech spacer (Study 2). METHODS: A randomised double-blind cross-over comparison was conducted. In Study 1, 27 adults with stable asthma who were currently using pressurised metered dose inhaler therapy attended for three study days. On each study day subjects inhaled doubling doses of histamine and were randomised to receive: (a) salbutamol 200 micrograms via Breath-A-Tech spacer and placebo 200 micrograms via Volumatic spacer; (b) placebo two puffs via Breath-A-Tech spacer and salbutamol 200 micrograms via Volumatic spacer; or (c) salbutamol 1 mg in 2 mL saline via jet nebuliser. FEV1 and FEF 25-75% were measured at two minute intervals for 20 minutes. In Study 2, subjects were randomised to use regular asthma medication by Volumatic or Breath-A-Tech spacers and recorded symptoms and peak expiratory flow (PEF) in a daily diary. RESULTS: Lung function improved from a baseline FEV1 of 51% predicted to 72% after salbutamol inhalation from each of the delivery systems. The spacers and nebulisers produced the same maximum improvement in FEV1, however, lung function improved more rapidly when salbutamol was delivered by spacer. There was no difference in asthma control comparing inhaler use via Breath-A-Tech with Volumatic spacer over two weeks use. Subject preference favoured the Breath-A-Tech spacer (72% vs 4%). CONCLUSIONS: The Volumatic and Breath-A-Tech spacer devices are effective delivery systems in asthma and may offer a more rapid response than jet nebulisation at a lower cost.
Adult↗
Addition of fexofenadine to inhaled corticosteroid therapy to reduce inflammatory biomarkers in atopic asthma.
BACKGROUND: We previously showed that H1-antihistamines may shift the PC20 (provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20%) threshold to adenosine monophosphate (AMP) challenge but may paradoxically prolong recovery. OBJECTIVES: To measure AMP recovery using a constant predetermined AMP PC20 and to evaluate whether fexofenadine use confers add-on effects to treatment with either fluticasone propionate alone or combined fluticasone propionate-salmeterol. METHODS: Fourteen atopic patients with mild-to-moderate asthma (forced expiratory volume in 1 second of 76%) completed a double-blind, randomized, crossover study consisting of 3-week treatment blocks of either fluticasone propionate-salmeterol, 250 microg twice daily, or fluticasone propionate alone, 250 microg twice daily, in conjunction with either fexofenadine, 180 mg once daily, or matched placebo. Recovery after a predetermined AMP PC20 challenge was measured (primary outcome), along with exhaled nitric oxide levels, plasma eosinophil cationic protein levels, peripheral eosinophil counts, pulmonary function, diary card outcomes, and quality of life (all secondary outcomes). RESULTS: There were no differences in any of the primary or secondary outcomes when fexofenadine was added to treatment with either fluticasone propionate-salmeterol or fluticasone propionate alone. The mean AMP recovery time was 25.0 vs 23.4 minutes for fexofenadine and placebo, respectively, as add-on to fluticasone-salmeterol and 22.5 vs 23.9 minutes, respectively, as add-on to fluticasone alone. CONCLUSION: Fexofenadine did not affect recovery to a fixed dose of AMP challenge or any other surrogate inflammatory markers when given as add-on therapy to corticosteroid-treatedatopic asthmatic patients.
Adenosine Monophosphate↗
An international perspective on anticholinergic therapy.
Since the introduction of inhaled quaternary anticholinergic bronchodilators, their clinical usefulness has been explored in a variety of settings. They have emerged as the inhaled bronchodilators of first choice in the management of chronic obstructive pulmonary disease (COPD). In other countries, they have also found an adjunctive role in the management of asthma. This may be best seen in the treatment of acute asthma where the combination of anticholinergic and adrenergic bronchodilators appear more effective than single-agent inhalation therapy. This finding appears consistently in large studies, whether in adult or pediatric populations. Such combination nebulizer therapy would appear to be cost effective, but further study is required.
Bronchodilator Agents↗
Combined therapy with inhaled nitric oxide and intravenous epoprostenol (prostacyclin) for critical pulmonary perfusion after the Fontan procedure.
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Administration, Inhalation↗
Effects of inhaled FK 506 on the suppression of acute rejection after lung transplantation: use of a rat orthotopic lung transplantation model.
BACKGROUND: FK 506 inhalant was recently developed for localized administration. We investigated its effects on acute lung allograft rejection and compared its efficacy with that of intramuscular administration of FK 506. METHODS: Rats (n = 123) with orthotopic left lung transplantation were divided into 9 groups. Six groups inhaled FK 506 (5 puffs, 10 puffs or 20 puffs per day), or were given intramuscular administration of FK 506 (0.05, 0.1 or 1.0 mg/kg/day). The other groups included rats receiving an isograft, rats with an untreated allograft, and a placebo group. All groups (n = 6 each) were monitored for 14 days post-operatively as an end-point and graft survival time was determined. The remaining animals were killed 4 days after transplantation. The histologic grade of rejection was determined for all groups (n = 6 each). With both (n = 3 each) inhalation therapy and intramuscular administration of FK 506, which showed similar degrees of effectiveness, both blood FK 506 concentration and cytokine expression in the graft and spleen were evaluated. RESULTS: FK 506 inhalation therapy extended allograft survival time and reduced histologic rejection on Day 4 in all groups. Graft survival time and histologic rejection scores at a dose of 10 puffs/day were comparable to those with 0.1 mg/kg/day of intramuscular FK 506. Trough concentrations of FK 506 in blood were detectable with 0.1 mg/kg/day of intramuscular FK 506, but not with 10 puffs/day. The messenger RNA expression levels of interferon-gamma in the lung allograft was suppressed significantly at a dose of 10 puffs/day. CONCLUSIONS: FK 506 inhalant enhances acute lung allograft survival with lower blood concentrations than when using comparable intramuscular administration.
Administration, Inhalation↗
Aerosolized pharmacotherapy in the neonate.
The use of aerosolized pharmacotherapy (inhalation therapy) in the intensive care nursery has been expanding since the first reports in the early 1980s. The potential benefits of this route of therapy include delivery of high concentrations of medicines directly to the respiratory system, avoiding the side effects of systemic administration. However, the anatomy and physiology of the newborn infant provide obstacles to inhalation therapy not encountered in older children and adults. A review of the literature reveals only limited data supporting the use of medications delivered by aerosolization in the neonate. A need for continued basic and clinical research in this area is apparent.
Administration, Inhalation↗
Improved asthma control with budesonide/formoterol in a single inhaler, compared with budesonide alone.
Budesonide/formoterol in a single inhaler was compared with budesonide alone, and with concurrent administration of budesonide and formoterol from separate inhalers, in patients with asthma, not controlled with inhaled glucocorticosteroids alone. In this 12-week, double-blind, randomized, double-dummy study, 362 adult asthmatics (forced expiratory volume in one second 73.8% of predicted, inhaled glucocorticosteroid dose 960 microg x day(-1)) received single inhaler budesonide/formoterol (Symbicort Turbuhaler) 160/4.5 microg, two inhalations b.i.d., or corresponding treatment with budesonide, or budesonide plus formoterol via separate inhalers. There was a greater increase in morning peak expiratory flow (PEF) with single-inhaler (35.7 L x min(-1)) and separate-inhaler (32.0 L x min(-1)) budesonide and formoterol, compared with budesonide alone (0.2 L x min(-1); p<0.001, both comparisons); the effect was apparent after 1 day (p<0.001 versus budesonide, both comparisons). Similarly, evening PEF, use of rescue medication, total asthma symptom scores and percentage of symptom-free days improved more with both single inhaler and separate inhaler therapy than with budesonide alone, as did asthma control days (approximately 15% more, p<0.001 versus budesonide, both comparisons, with a marked increase in the first week). All treatments were well tolerated and the adverse event profile was similar in all three treatment groups. It is concluded that single inhaler therapy with budesonide and formoterol is a clinically effective and well-tolerated treatment for patients with asthma that is not fully controlled by inhaled glucocorticosteroids alone.
Administration, Inhalation↗
[Respiratory training, breathing exercises, aerosol therapy and inhalation respiration].
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Aerosols↗
First approved inhaled insulin therapy for diabetes mellitus.
The long-term benefits of tight glycemic control in preventing microvascular and macrovascular complications are well established in both Type 1 diabetes mellitus (Type 1 DM) and Type 2 diabetes mellitus (Type 2 DM). Nonetheless, achievement of recommended haemoglobin A1c (HbA(1c)) goals (< or = 6.5 - 7.0%) has remained elusive, especially in patients with diabetes who require insulin therapy. Delayed/suboptimal titration of insulin is partly related to poor acceptance of multiple injection regimen by both physicians and patients. EXUBERA (human insulin [rDNA origin]; Pfizer), the first approved inhaled insulin for the treatment of diabetic patients, has been shown to be safe and as effective as regular/rapidly acting insulin in improving glycemic control. In addition to controlling postprandial glucose excursions, EXUBERA exerts a major action to reduce fasting plasma glucose (FPG) concentration. Thus, it has the potential to be used as a monotherapy in Type 2 DM, as well as in combination with an insulin sensitizer in Type 2 DM or in combination with long-acting insulin in both Type 2 DM and Type 1 DM.
Administration, Inhalation↗
Polyethyleneimine-based gene therapy by inhalation.
The delivery of genes by inhalation holds promise for the treatment of a wide range of pulmonary and non-pulmonary disorders and offers numerous advantages over more invasive modes of delivery. Subsequent to the cloning of the cystic fibrosis gene, there was great interest in the delivery of genes directly to the lung surfaces by aerosol, and most early efforts focused on the use of non-viral vectors, particularly cationic lipids. Unfortunately, nebulisation shear forces, inefficient penetration of mucous barriers and inhibitory effects of surfactant and other lung-specific features have generally resulted in a lack of therapeutic effect, and much of this work has diminished in recent years as a consequence. Polyethyleneimine (PEI)-based formulations have proven stable during nebulisation and result in nearly 100% efficient transfection throughout the airways, as well as significant, although lower, levels of transfection throughout the lung parenchyma. Most importantly, therapeutic responses have been obtained in several animal lung tumour models when PEI-based complexes of p53 and IL-12 genes were delivered by aerosol. This approach may also prove useful as a means of localised genetic immunisation. In addition, this mode of delivery seems to be associated with surprisingly low toxicity, and results in little or no CpG immunostimulatory response, which has presented a challenge to repeated gene therapy via other modes of delivery.
Adjuvants, Immunologic↗
Comparison of the effectiveness of inhaler devices in asthma and chronic obstructive airways disease: a systematic review of the literature.
BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are common diseases of the airways and lungs that have a major impact on the health of the population. The mainstay of treatment is by inhalation of medication to the site of the disease process. This can be achieved by a number of different device types, which have wide variations in costs to the health service. A number of different inhalation devices are available. The pressurised metered-dose inhaler (pMDI) is the most commonly used and cheapest device, which may also be used in conjunction with a spacer device. Newer chlorofluorocarbons (CFC)-free inhaler devices using hydrofluoroalkanes (HFAs) have also been developed. The drug is dissolved or suspended in the propellant under pressure. When activated, a valve system releases a metered volume of drug and propellant. Other devices include breath-actuated pMDIs (BA-pMDI), such as Autohaler and Easi-Breathe. They incorporate a mechanism activated during inhalation that triggers the metered-dose inhaler. Dry powder inhalers (DPI), such as Turbohaler, Diskhaler, Accuhaler and Rotahaler, are activated by inspiration by the patient. The powdered drug is dispersed into particles by the inspiration. With nebulisers oxygen, compressed air, or ultrasonic power is used to break up solutions or suspensions of medication into droplets for inhalation. The aerosol is administered by mask or by a mouthpiece. There has been no previous systematic review of the evidence of clinical effectiveness and cost-effectiveness of these different inhaler devices. OBJECTIVES: To review systematically the clinical effectiveness and cost-effectiveness of inhaler devices in asthma and COPD. METHODS: The different aspects of inhaler devices were separated into the most clinically relevant comparisons. Methods involved systematic searching of electronic databases and bibliographies for randomised controlled trials (RCTs) and systematic reviews. Pharmaceutical companies and experts in the field were contacted for further information. Trials that met the inclusion criteria were appraised and data extraction was under-taken by one reviewer and checked by a second reviewer, with any discrepancies being resolved through agreement. RESULTS--IN VITRO CHARACTERISTICS VERSUS IN VIVO TESTING AND CLINICAL RESPONSE: There is evidence that when comparative testing is performed on inhaler devices using the same methods, there is some correlation between particle size measurements and clinical response. However, the measurements are dependent upon the methods used, and a single measure of a device in isolation is of limited value. Also, there is little data on comparing devices of different types. There is currently insufficient data to verify the ability of in vitro assessments to predict inhaler performance in vivo. RESULTS--EFFECTIVENESS OF METERED-DOSE INHALERS FOR THE DELIVERY OF CORTICOSTEROIDS IN ASTHMA: The review of three trials in children and 21 trials in adults demonstrated no evidence to suggest clinical benefits of any other inhaler device over a pMDI in corticosteroid delivery. RESULTS--EFFECTIVENESS OF METERED-DOSE INHALERS FOR THE DELIVERY OF BETA-AGONISTS IN STABLE ASTHMA: In children, 11 studies were reviewed, of which seven compared the Turbohaler with the pMDI. One study found a significant treatment difference in peak expiratory flow rate, although there were differences in the patients' baseline characteristics. In adults, a review of 70 studies found no demonstrable difference in the clinical bronchodilator effect of short-acting b2-agonists delivered by the standard pMDI compared with that produced by any other DPI, HFA-pMDI or the Autohaler device. The finding that HFA-pMDIs may reduce treatment failure and oral steroid requirement in beta-agonist delivery needs further confirmatory research in adequately randomised clinical trials. RESULTS--EFFECTIVENESS OF NEBULISERS VERSUS METERED-DOSE INHALERS FOR THE DELIVERY OF BRONCHODILATORS IN STABLE ASTHMA: In children, three included trials compared different devices with a nebuliser and demonstrated no evidence of clinical superiority of nebulisers over inhaler devices in bronchodilator delivery. A total of 23 studies in adults found no equivalence for the main pulmonary outcomes and no evidence of difference in other outcomes. RESULTS--EFFECTIVENESS OF METERED-DOSE INHALERS FOR THE DELIVERY OF BETA-AGONISTS IN COPD: Only two studies were included in this review. No evidence of clinical difference was found in beta-agonist delivery. RESULTS--EFFECTIVENESS OF NEBULISERS VERSUS METERED-DOSE INHALERS FOR THE DELIVERY OF BRONCHODILATORS IN COPD: Evidence from 14 trials demonstrated equivalence for the main outcomes of pulmonary function. For other outcomes there was no evidence of treatment difference in bronchodilator delivery. RESULTS--PATIENTS' ABILITY TO USE METERED-DOSE INHALERS: Differences among studies and the heterogeneity of the results make it difficult to draw conclusions about inhaler technique differences between device types. The review of technique after teaching the correct technique suggests that there is no difference in patients' ability to use DPI or pMDIs. RESULTS--ECONOMIC ANALYSIS: The total number of NHS prescriptions for inhaler therapy for asthma in 1998 was over 31 million, with a net ingredient cost in excess of 392 million GB pounds. This economic assessment uses decision analysis to estimate the relative cost-effectiveness of inhaler devices for the delivery of bronchodilator and corticosteroid inhaled therapy. Overall, there were no differences in patient outcomes among the devices. On the assumption that the devices were clinically equivalent, pMDIs were the most cost-effective devices for asthma treatment. CONCLUSIONS: This systematic review examined the evidence from clinical trials evaluating the clinical effectiveness of different inhaler devices in the delivery of inhaled corticosteroids and beta2-bronchodilators for patients with asthma and COPD. The evidence from the published clinical literature demonstrates no difference in clinical effectiveness between nebulisers and alternative inhaler devices compared to standard pMDI with or without a spacer device. The cost-effectiveness evidence therefore favours pMDIs (or the cheapest inhaler device) as first-line treatment in all patients with stable asthma unless other specific reasons are identified. Patients can use pMDIs as effectively as other inhaler devices as long as the correct inhalation technique is taught. CONCLUSIONS--RECOMMENDATIONS FOR RESEARCH: Further clinical trials are required to demonstrate any differences in the clinical effectiveness and cost-effectiveness of inhaler devices and nebulisers compared with pMDIs. These should be of sufficient statistical power and methodological rigour to demonstrate any clinical benefit. Trials should be undertaken in community settings to ensure the generalisability of results. Outcome measures should be more patient-centred and report adverse effects more completely. Reporting of data from trials should be improved.
Adolescent↗
Controversies in the use of inhaled nitric oxide therapy in the newborn.
Inhaled nitric oxide (NO) causes sustained improvement in oxygenation in near-term and term newborns with persistent pulmonary hypertension of the newborn (PPHN), and reduces the need for extracorporeal membrane oxygenation (ECMO). However, many questions remain concerning the application of inhaled NO to less severely ill infants, its use in units without immediate access to adjuvant therapies for hypoxemic respiratory failure, and in centers without ECMO. Particular vigilance must be given to the potential impact of widespread dissemination on inhaled NO therapy on time ECMO initiation, and the inappropriate use of inhaled NO in premature neonates.
Administration, Inhalation↗