Surfactants in Acute Respiratory Distress Syndrome in Infants and Children: Past, Present and Future.

There is a lack of definitive data on the effective management of acute respiratory distress syndrome (ARDS) in infants and children. The development and validation of the Berlin definition (BD) for ARDS and the Pediatric Acute Lung Injury Consensus Conference (PALICC) recommendations in children represented a major advance in optimizing research and treatment, mainly due to the introduction of a severe ARDS category. Proposed reasons for the lack of consistent results with surfactants in children and infants compared with neonates include different causes, type of lung damage (direct or indirect), timing and mode of administration as well as the type of surfactant used. Secretory phospholipase A2 plays an important role in inflammation and possible dysfunction of surfactants in ARDS. Bronchoalveolar lavage (BAL) with normal saline and surfactant allows the removal of inhaled material, the recruitment of non-ventilating areas and the maintenance of the surfactant pool size. BAL with diluted surfactant allows rapid absorption of the surfactant at the air/liquid interface, which blocks the progression of pathological lung disease and in turn disrupts the inflammatory cycle. Importantly, it is now recognized that the type of surfactant, the time of administration and the method of administration could all play an important role in the management of ARDS, and there is evidence that surfactant is effective and well tolerated in children and infants with ARDS.

Lung function comparison between two decades in cystic fibrosis children: A single centre study.

OBJECTIVES: The purpose of this study was to compare two cohorts of cystic fibrosis (CF) patients born and treated in two different decades, diagnosed through a CF neonatal screening program. METHODOLOGY: We compared pulmonary function decline from 10 to 15 years of age in patients with cystic fibrosis born between 1979 and 1984 (Cohort 1) and between 1991 and 1996 (Cohort 2). Forced expiratory volume in 1 sec (FEV1%) and forced expiratory flow from 25% to 75% (FEF 25-75%) were analyzed by a linear mixed model approach. The differences between the two cohorts were estimated and the overall cohort effect was tested. RESULTS: Ninety-two patients (51 males, 41 females) fulfilled the selection criteria. Pancreatic insufficiency and CF related diabetes were present in 91% and 20% of patients, respectively. The mean absolute decrement of FEV1% was 9.2 (standard deviation [SD] 11.2) in Cohort 1 and 0.6 (SD 10.4) in Cohort 2 (P < 0.001). The mean decrement of FEF 25-75% was 16.3 (SD 19.5) in Cohort 1 and 1.3 (SD 16.8) in Cohort 2 (P < 0.001) and the Pseudomonas aeruginosa (Pa) colonization was 28% and 15% respectively (P = 0.1). CONCLUSIONS: Our results show that pulmonary function has clearly ameliorated over a decade in young CF patients, in a period during which several significant therapeutic changes have been introduced, such as dornase alfa, tobramycin and hypertonic saline. To our knowledge this is the first study showing a cohort effect in patients diagnosed after neonatal screening.

Analysis of the cost-effectiveness of surfactant treatment (Curosurf®) in respiratory distress syndrome therapy in preterm infants: early treatment compared to late treatment.

BACKGROUND: The best criteria for surfactant treatment in the perinatal period are unknown and this makes it of interest to consider the possible economic implications of lessening the use of more restrictive criteria. OBJECTIVE: The objective of this study is the evaluation of the costs of respiratory care for preterm infants with Respiratory Distress Syndrome (RDS) treated with "early rescue" surfactant compared to a "late rescue" strategy. METHODS: The study was carried out applying the costs of materials used, of staff and pharmacological therapy calculated in the Neonatal Intensive Care Unit (NICU) of an Italian hospital to the Verder et al. study (Pediatrics 1999) clinical data. RESULTS: The cost for patients treated with early strategy was slightly lower than for patients treated with late strategy (Euro 4,901.70 vs. Euro 4,960.07). The cost of treatment with surfactant was greater in the early group (Euro 458.49 vs. Euro 311.74), but this was compensated by the greater cost of treatment with Mechanical Ventilation (MV) in the late group (respectively Euro 108.85 vs. Euro 259.25). CONCLUSIONS: The cost-effectiveness analysis performed in this study shows how early treatment with surfactant in preterm infants with RDS, as well as being clinically more effective, is associated with a slightly lower cost.

Efficacy and safety of delapril/indapamide compared to different ACE-inhibitor/hydrochlorothiazide combinations: a meta-analysis.

The main objective of this meta-analysis was to compare the efficacy of the combination of delapril and indapamide (D+I) to different angiotensin-converting enzyme inhibitor (ACEi) plus hydrochlorothiazide (HCTZ) combinations for the treatment of mild-to-moderate hypertension. A secondary objective was to examine the safety of these two combinations. Studies comparing the efficacy of D+I to ACEi+HCTZ combinations in hypertensive patients and published on computerized databases (1974-2010) were considered. Endpoints included percentage of normalized patients, of responders, change in diastolic and systolic blood pressure (DBP/SBP) at different time-points, percentage of adverse events (AEs), and percentage of withdrawal. Four head-to-head randomized controlled trials (D+I-treated, n = 643; ACEi+HCTZ-treated, n = 629) were included. Meta-analysis indicated that D+I-treated patients had a higher proportion with normalized blood pressure (P = 0.024) or responders (P = 0.002) compared to ACEi+HCTZ-treated patients. No difference was observed between treatments on absolute values of DBP and SBP at different time-points. Although the rate of patients reporting at least one AE was similar in both groups (10.4% versus 9.9%), events leading to study withdrawal were lower in the D+I group versus the ACEi+HCTZ group (2.3% versus 4.8%, respectively; P = 0.018). This meta-analysis suggests that treatment with D+I could provide a higher proportion of normalized or responder patients with good tolerability compared to ACEi+HCTZ combinations.

Combination delapril/manidipine as antihypertensive therapy in high-risk patients.

The majority of patients with hypertension, and in particular high-risk patients or those with diabetes mellitus or renal dysfunction, are likely to require combination therapy with at least two antihypertensive agents (from different classes) to achieve their blood pressure (BP) target. The delapril/manidipine fixed-dose combination consists of two antihypertensive agents with different, yet complementary, mechanisms of action. Delapril/manidipine has demonstrated short- and long-term antihypertensive efficacy in a number of clinical studies in patients with hypertension with an inadequate response to monotherapy. Comparative studies have demonstrated that delapril/manidipine is as effective as enalapril/hydrochlorothiazide (HCTZ) in patients with hypertension with an inadequate response to monotherapy, and as effective as irbesartan/HCTZ, losartan/HCTZ, olmesartan medoxomil/HCTZ, ramipril/HCTZ and valsartan/HCTZ in reducing BP in patients with hypertension and diabetes, or in obese patients with hypertension. Therapy with delapril/manidipine also appears to exert beneficial effects that extend beyond a reduction in BP, including nephroprotective activity and an improvement in fibrinolytic balance, supporting its value as a treatment option in these patient populations at high or very high cardiovascular risk because of the presence of organ damage, diabetes or renal disease.