Recombinant Human Deoxyribonuclease Treatment in Hospital Management of Infants with Moderate-Severe Bronchiolitis

Abstract

Bronchiolitis is the main cause of respiratory insufficiency in infants, characterized by acute inflammation, edema, necrosis of epithelial cells and increased mucus production. Mucus is mainly purulent and consequently rich in DNA, as derived from nuclei of degenerating neutrophils and epithelial debris. The treatment is mainly supportive; bronchodilators and systemic steroids are often used but do not reduce the length of hospital stay. The aim of our study is to evaluate the efficacy of recombinant human DNase (rhDNase), in infants affected by moderate-severe bronchiolitis. In a randomized doubleblind placebo-controlled study, twenty-two infants (12 males) under 6 months of age (median age 1.6 months) were enrolled and randomly assigned to receive either nebulized rhDNase or placebo (saline) at a dose of 2.5 ml once a day for three days. All infants were evaluated, based on a clinical assessment Score, on admission and four times daily during the hospitalization. Placebo and study groups were sex-and age-matched and were similar in terms of clinical severity on admission. No differences were observed between the two groups of patients with regard to the length of hospitalization and clinical score during the days observed. Two out of four infants, all in the study group, presenting atelectasis on chest radiographs, showed a rapid improvement on the first day. RhDNase is not an effective routine therapy in treating infants hospitalized for bronchiolitis and it is not useful in preventing severe forms of the disease. On the contrary, it may be an effective, safe and cost-benefit treatment only in infants with bronchiolitis and massive atelectasis.

Neutrophil extracellular traps cause airway obstruction during respiratory syncytial virus disease

“…Addition of DNA to mucus increases viscosity in vitro . In this context, some studies have assessed the effects of nebulized recombinant DNase in children with RSV–LRTD to reduce mucus viscosity and decrease airway obstruction . One clinical trial showed strong radiological improvement and one case‐series in mechanically ventilated infants with severe RSV–LRTD showed clinical and radiological improvement .…”

“…One clinical trial showed strong radiological improvement [10] and one case-series in mechanically ventilated infants with severe RSV-LRTD showed clinical and radiological improvement [46]. Unfortunately, in two more recent randomized, placebo-controlled trials, DNase treatment did not reduce the duration of admission or oxygen need of hospitalized infants with RSV-LRTD [47,48]. However, it is possible that this negative result is related to the relatively mild RSV disease in the populations studied, or to the difficulty for the agent to reach the more distal and heterogeneous distributed airway plugs.…”

Viral bronchiolitis in children: A common condition with few therapeutic options

“…The therapy for bronchiolitis is mainly supportive [5], with supplemental oxygen, nasal washing, and intravenous (IV) fluids. Clinical trials, testing β 2-agonists [6,7], glucocorticoids [8], epinephrine [9], recombinant human DNase [10,11], and hypertonic saline [12] in bronchiolitis report highly controversial results.…”

Immunopathogenetic and Pharmacological Aspects of Interstitial Lung Diseases

“…I.e); 6) lymphoid interstitial pneumonia (LIP), characterized by lymphoid and plasma cellular infiltration of alveolar septa and peribronchiolar and periarteriolar interstitium; 7) giant cell interstitial pneumonia (GIP) is less common than the others and has a lymphocytic and plasmacytic infiltrate with giant cells in alveoli in a great phagocytic activity and they can be, in fact, defined as cannibal. These types, more than autonomous entities, are considered different evolutive phases of an interstitial reaction to equal stimuli or expressions of a lung change as a reaction to damaging agents of different kinds (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Another classification links interstitial lung diseases with more or less homogeneous aetiological factors, marking two main groups: a) interstitial lung diseases of known aetiology (infective agents, organic dusts, inorganic dusts, chemical dusts, gases, fumes, exhalations, aerosols, poisons, ionizing radiations, medicines); b) interstitial lung diseases of unknown aetiology (familiar and sporadic idiopathic lung fibrosis, collagen-vascular diseases, sarcoidosis, histiocytosis X, Goodpasture syndrome, eosinophilic pneumonia, lymphangioleiomyomatosis, hereditary diseases, infiltrative lymphocytic diseases, lung vasculitis, idiopathic lung haemosiderosis, alveolar proteinosis, lower airways diseases, Weber-Christian disease, hypereosinophilic syndromes, lung veinocclusive disease, lung carcinomatous lymphangitis, haemodynamic changes, chronic kidney failure, gastro-esophageal reflux with chronic aspiration, bowel diseases, liver diseases) and a newer one considers: I) idiopathic interstitial pneumonias 2) environmental and occupational diseases 3) multisystem diseases 4) rare lung diseases.…”