Inhaled hypertonic saline in infants and toddlers with cystic fibrosis: short‐term tolerability, adherence, and safety

Rosenfeld, Margaret; Davis, Stephanie D.; Brumback, Lyndia C.; Daniel, Stephen; Rowbotham, Ron; Johnson, Robert P.; McNamara, Sharon; Jensen, Renée; Barlow, Carol; Ratjen, Félix

doi:10.1002/ppul.21425

Cited by 30 publications

(21 citation statements)

References 28 publications

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“…Our data from neonatal bENaC-overexpressing mice demonstrate directly that airway surface rehydration with HS is effective in preventing the development of mucus obstruction in vivo. These results, together with safety data in infants and young children (19,41), suggest inhaled HS as an inexpensive and safe preventive treatment for infants with CF. Consequently, the potential benefits of this preventive strategy should be further explored in clinical trials that include morphological and functional surrogate endpoints that are more sensitive and more specific in capturing treatment responses in early obstructive airways disease (36, 38-40, 42, 43).…”

Section: Discussionmentioning

confidence: 92%

Hypertonic Saline Is Effective in the Prevention and Treatment of Mucus Obstruction, but Not Airway Inflammation, in Mice with Chronic Obstructive Lung Disease

Graeber

Zhou-Suckow

Schatterny

et al. 2013

Am J Respir Cell Mol Biol

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Recent evidence suggests that inadequate hydration of airway surfaces is a common mechanism in the pathogenesis of airway mucus obstruction. Inhaled hypertonic saline (HS) induces osmotic water flux, improving hydration of airway surfaces. However, trials in patients with obstructive lung diseases are limited. The aim of this study was to investigate effects of HS on mucus obstruction and airway inflammation in the prevention and treatment of obstructive lung disease in vivo. We, therefore, used the b-epithelial Na 1 channel (bENaC)-overexpressing mouse as a model of chronic obstructive lung disease and determined effects of preventive and late therapy with 3% HS and 7% HS on pulmonary mortality, airway mucus obstruction, and inflammation. We found that preventive treatment with 3% HS and 7% HS improved growth, reduced mortality, and reduced mucus obstruction in neonatal bENaC-overexpressing mice. In adult bENaC-overexpressing mice with chronic lung disease, mucus obstruction was significantly reduced by 7% HS, but not by 3% HS. Treatment with HS triggered airway inflammation with elevated keratinocyte chemoattractant levels and neutrophils in airways from wild-type mice, but reduced keratinocyte chemoattractant in chronic neutrophilic inflammation in adult bENaCoverexpressing mice. Our data demonstrate that airway surface rehydration with HS provides an effective preventive and late therapy of mucus obstruction with no consistent effects on inflammation in chronic lung disease. These results suggest that, through mucokinetic effects, HS may be beneficial for patients with a spectrum of obstructive lung diseases, and that additional strategies are required for effective treatment of associated airway inflammation.

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Section: Discussionmentioning

confidence: 92%

Hypertonic Saline Is Effective in the Prevention and Treatment of Mucus Obstruction, but Not Airway Inflammation, in Mice with Chronic Obstructive Lung Disease

Graeber

Zhou-Suckow

Schatterny

et al. 2013

Am J Respir Cell Mol Biol

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“…The most common side effects are increased cough, chest tightness, bronchospasm, throat irritation and a temporary decline in FEV 1 (26,27). In this trial, we added salbutamol to prevent possible bronchial constriction.…”

Section: Discussionmentioning

confidence: 99%

Comparing the Efficacy of 7%, 3% and 0.9% Saline in Moderate to Severe Bronchiolitis in Infants

et al. 2016

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Background:There is no standard treatment option in acute bronchiolitis. 3-7% hypertonic saline (HS) seems to be the effective treatment choice for reducing the hospitalization day. Aims: To compare the effect of nebulized 7% HS/ salbutamol and 3% HS/salbutamol to 0.9% saline/ salbutamol. The primary outcome measure was the effect of study drugs on the length of hospital stay (LOS). Secondary outcome measures were safety and efficacy in reducing the clinical severity score (CSS) at the 24 hours of the study. Study Design: Prospective, double-blinded randomized clinical study. Methods: The study consists of 104 infants. Groups were constituted according to the treatment they received: These are, group A -0.9% saline/salbutamol, group B -3% HS/salbutamol and group C-7% HS/salbutamol. Heart beat, Bronchiolitis CSS and oxygen saturation of the patients were determined before and after nebulization. The patients were monitored for adverse reactions. Results: Length of hospital stay in group A, B and C were as follows; 72.0 (20-288) hours in group A, 64.0 (12-168) hours in group B and 60.0 (12-264) hours in group C. No significant differences was observed among three groups (p>0.05). Conclusion: 7% HS and 3% HS does not have any effect to decrease LOS for infants with bronchiolitis. Keywords: Bronchiolitis, hypertonic saline, infant Copyright 2016 © Trakya University Faculty of Medicine Balkan Med J 201633:193-7 Comparing Bronchiolitis is the most frequent viral lower respiratory tract infection seen in infancy period characterized by cough, wheezing and tachypnea. Bronchiolitis is the major reason of infant hospitalization in both developed and developing countries. Although it is common there is no current standard treatment. Supportive care is the only evidence based treatment option (1,2). Many studies focused on testing the effects of bronchodilators such as β2-agonsits (3), epinephrine (4), glucocorticoids (5) and magnesium sulfate (6) with controversial results.There exists the first necrosis of the respiratory epithelium in bronchiolitis. Following by the fact that, exaggerated mucus production occurs due to the proliferation of goblet cells. On the other hand epithelial regeneration with nonciliated cells happens thus decreasing mucociliary clearance. Lymphocytic infiltration may result in submucosal edema (7). Johnson et al. (7) demonstrated that, airway obstruction in bronchiolitis was because of epithelial and inflammatory cell debris. And they did not observe bronchial smooth muscle constriction. This can explain why bronchodilator therapy is not effective in bronchiolitis. Thus the ideal treatment has to decrease submucosal edema and improve mucociliary clearance by restoring the elasticity and viscosity of the mucus. In the last decade, 3% and 5% hypertonic saline (HS) studied in infants with bronchiolitis with good results (8)(9)(10)(11)(12)(13)(14). In the light of cystic fibrosis studies, it was shown that 7% HS increases mucociliary clearance and decreases epithelial edema (15-17). Thus,

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“…Only one study reported on new development of BHR to HS in one participant at the end of a 2-weeks trial [67]. However, Elkins et al found cough to resolve after a mean of 15 days [62].…”

Section: Hypertonic Salinementioning

confidence: 99%

“…Nebulized HS can induce acute airway narrowing or bronchospasm and cough (Supplementary Tables 2), [11,[55][56][57][58][59][60][61][62][63][64][65][66][67][68][69] but in most cases these symptoms decrease after a few weeks so that the majority of patients find HS tolerable [55,62,63,68]. Rodwell et al were the first to describe acute airway responsiveness to inhaled 10% saline in a group of CF subjects with asthma-like symptoms [11].…”

Section: Hypertonic Salinementioning

confidence: 99%

Bronchial Hyperreactivity Related to Inhalation Therapy in Cystic Fibrosis Patients

Eyns¹

2014

J Pulm Respir Med

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It is presumed that bronchial hyperreactivity (BHR) can occur with any inhaled agent and may be a reason for discontinuation of inhalation therapy in cystic fibrosis (CF) patients. On the other hand, inhalation of antibiotics is being increasingly used to eradicate or treat infections.This review focuses on identifying the mechanisms of BHR for a better understanding of its impact on inhalation treatment. BHR in CF is suggested to be secondary to underlying airway disease (associated to poor pulmonary function, chronic inflammation and aerosol distribution) or to be a separate condition occurring more in CF. Furthermore, certain characteristics of the aerosol solution itself, such as the active molecule, chemical additives and particle size, can cause BHR.Recombinant human DNase (rhDNase), hypertonic saline (HS) and the antibiotics tobramycin, colistin and aztreonam lysine for inhalation (AZLI) are frequently used inhalation drugs in the treatment of CF. Prevalence of BHR related to both short and long-term inhalation of these drugs as reported in the literature was investigated. Acute BHR is documented in up to two thirds of CF patients. Despite the widespread use of rhDNase, HS, tobramycin, colistin and AZLI, only one long-term trial looked for, but did not demonstrate, BHR at the end of the trial period.

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Inhaled hypertonic saline in infants and toddlers with cystic fibrosis: short‐term tolerability, adherence, and safety

Cited by 30 publications

References 28 publications

Hypertonic Saline Is Effective in the Prevention and Treatment of Mucus Obstruction, but Not Airway Inflammation, in Mice with Chronic Obstructive Lung Disease

Hypertonic Saline Is Effective in the Prevention and Treatment of Mucus Obstruction, but Not Airway Inflammation, in Mice with Chronic Obstructive Lung Disease

Comparing the Efficacy of 7%, 3% and 0.9% Saline in Moderate to Severe Bronchiolitis in Infants

Bronchial Hyperreactivity Related to Inhalation Therapy in Cystic Fibrosis Patients

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