Respiratory rate in infants with cystic fibrosis throughout the first year of life and association with lung clearance index measured shortly after birth.

BACKGROUND: Lung impairment in cystic fibrosis (CF) starts in infancy. However, tools to monitor early lung disease are limited. Respiratory rate (RR) as a key vital sign is easy to assess during sleep and is elevated during acute respiratory disease. Thus, elevated RR could indicate early lung impairment and potentially serve as a diagnostic tool in disease monitoring. METHODS: In a prospective cohort of infants with CF diagnosed by newborn screening and healthy controls RR was measured and respiratory symptoms reported weekly throughout infancy. Infants performed a lung function measurement within the first weeks of life. RESULTS: The analyses included 5656 measurements from 153 infants (43 with CF). RR declined from 43.2 (40.5)/min at 6 weeks of age to 28.3 (24.6)/min at 50 weeks in infants with CF (healthy controls). Infants with CF had consistently higher RR than controls (mean difference: 4.15/min; (95% CI 2.86-5.44); p < .001). In both study groups, RR was increased throughout the study period in infants with higher lung clearance indices (LCI) and during episodes of respiratory infections. CONCLUSIONS: Infants with CF have a higher RR compared to healthy controls during the first year of life. The association with early LCI measurements, the current gold standard to assess physiology of peripheral airways persisted throughout the study period. This may indicate tracking of lung function by RR. It might thus be an early subtle sign of functional respiratory deficit. Further studies will show if RR can be used as a sensitive and promising marker to monitor early CF lung disease.

Modifiable risk factors associated with bronchiolitis.

BACKGROUND: We sought to clarify possibly modifiable risk factors related to pollution responsible for acute bronchiolitis in hospitalized infants. METHODS: For this observational study, we recruited 213 consecutive infants with bronchiolitis (cases: median age: 2 months; age range: 0.5-12 months; boys: 55.4%) and 213 children aged <3 years (controls: median age: 12 months; age range: 0.5-36 months; boys: 54.5%) with a negative medical history for lower respiratory tract diseases hospitalized at 'Sapienza' University Rome and IRCCS Bambino Gesù Hospital. Infants' parents completed a standardized 53-item questionnaire seeking information on social-demographic and clinical characteristics, indoor pollution, eating habits and outdoor air pollution. Multivariate logistic regression analyses were run to assess the independent effect of risk factors, accounting for confounders and effect modifiers. RESULTS: In the 213 hospitalized infants the questionnaire identified the following risk factors for acute bronchiolitis: breastfeeding ⩾3 months (OR: 2.1, 95% confidence interval [CI]: 1.2-3.6), presence of older siblings (OR: 2.8, 95% CI: 1.7-4.7), ⩾4 cohabitants (OR: 1.5, 95% CI: 1.1-2.1), and using seed oil for cooking (OR: 1.7, 95% CI: 1.2-2.6). Having renovated their home in the past 12 months and concurrently being exposed daily to smoking, involving more than 11 cigarettes and two or more smoking cohabitants, were more frequent factors in cases than in controls ( p = 0.021 and 0.05), whereas self-estimated proximity to road and traffic was similar in the two groups. CONCLUSIONS: We identified several risk factors for acute bronchiolitis related to indoor and outdoor pollution, including inhaling cooking oil fumes. Having this information would help public health authorities draw up effective preventive measures - for example, teach mothers to avoid handling their child when they have a cold and eliminate exposure to second-hand tobacco smoke.

Risk Factors for Virus-induced Acute Respiratory Tract Infections in Children Younger Than 3 Years and Recurrent Wheezing at 36 Months Follow-Up After Discharge.

BACKGROUND: We sought to know more about how 14 common respiratory viruses manifest clinically, and to identify risk factors for specific virus-induced acute respiratory tract infections (ARTIs) in children younger than 3 years old and for wheezing at 36-month follow-up. METHODS: We retrospectively studied the clinical records for 273 full-term children (median age, 2.9 months; range, 0.26-39; boys, 61.2%) hospitalized for ARTIs, whose nasopharyngeal specimen tested positive for a respiratory virus and 101 children with no history of respiratory diseases (median age, 8 months; range, 0.5-36.5; boys, 58.4%). At 12, 24 and 36 months after children's discharge, all parents were interviewed by telephone with a structured questionnaire on wheezing episodes. RESULTS: The most frequently detected viruses were respiratory syncytial virus in bronchiolitis, human rhinovirus in pneumonia and human bocavirus in wheezing. Multivariate analysis identified, as risk factors for virus-induced ARTIs, the presence of siblings [odds ratio (OR): 3.0 (95% confidence interval [CI]: 1.8-5.2)], smoking cohabitants (OR: 2.3 (95% CI: 2-4.2)] and breastfeeding lasting less than 3 months [OR: 0.5 (95% CI: 0.3-0.9)]. The major risk factor for respiratory syncytial virus-induced ARTIs was exposure to tobacco smoke [OR: 1.8 (95% CI: 1.1-3.2)]. Risk factors for human rhinovirus-induced ARTIs were attending day-care [OR: 5.0 (95% CI: 2.3-10.6)] and high eosinophil blood counts [OR: 2.6 (95% CI: 1.2-5.7)]. The leading risk factor for recurrent wheezing was exposure to tobacco smoke [OR: 2.5 (95% CI: 1.1-15.6)]. CONCLUSIONS: Each respiratory virus leads to a specific clinical manifestation. Avoiding exposing children to tobacco smoke might restrict viral spread from sick parents and siblings to younger children, prevent severe respiratory diseases, and possibly limit sequelae.

Rhinovirus Infections and Associated Respiratory Morbidity in Infants: A Prospective Cohort Study.

BACKGROUND: Risk factors promoting rhinovirus (RV) infections are inadequately described in healthy populations, especially infants. OBJECTIVES: To determine the frequency of symptomatic and asymptomatic RV infections and identify possible risk factors from host and environment among otherwise healthy infants. METHODS: In a prospective birth cohort, respiratory health was assessed in 41 term-born infants by weekly telephonic interviews during the first year of life, and weekly nasal swabs were collected to determine RV prevalence. In a multilevel logistic regression model, associations between prevalence and respiratory symptoms during RV infections and host/environmental factors were determined. RESULTS: Twenty-seven percent of nasal swabs in 41 infants tested positive for RVs. Risk factors for RV prevalence were autumn months [odds ratio (OR) = 1.71, P = 0.01, 95% confidence interval (CI): 1.13-2.61], outdoor temperatures between 5 and 10°C (OR = 2.33, P = 0.001, 95% CI: 1.41-3.86), older siblings (OR = 2.60, P = 0.001, 95% CI: 1.50-4.51) and childcare attendance (OR = 1.53, P = 0.07, 95% CI: 0.96-2.44). Fifty-one percent of RV-positive samples were asymptomatic. Respiratory symptoms during RV infections were less likely during the first 3 months of life (OR = 0.34, P = 0.003, 95% CI: 0.17-0.69) and in infants with atopic mothers (OR = 0.44, P = 0.008, 95% CI: 0.24-0.80). Increased tidal volume (OR = 1.67, P = 0.03, 95% CI: 1.04-2.68) and outdoor temperatures between 2 and 5°C (OR = 2.79, P = 0.02, 95% CI: 1.17-6.61) were associated with more symptoms. CONCLUSIONS: RVs are highly prevalent during the first year of life, and most infections are asymptomatic. Frequency of RV infections is associated with environmental factors, while respiratory symptoms during RV infections are linked to host determinants like infant age, maternal atopy or premorbid lung function.

Bronchiolitis: Analysis of 10 consecutive epidemic seasons.

Bronchiolitis is the leading cause of hospitalization in infants under 12 months. Our aims were to analyze epidemiological characteristics of infants with bronchiolitis over 10 consecutive seasons and to evaluate whether there are any clinical differences between infants hospitalized for bronchiolitis during epidemic peak months and infants in non-peak months. We enrolled consecutive enrolled 723 previously healthy term infants hospitalized at the Paediatric Emergency Department, "Sapienza" University of Rome over the period 2004-2014. Fourteen respiratory viruses were detected from nasopharyngeal aspirates by molecular methods. Clinical and demographic data were extracted from clinical charts. Viruses were detected in 351 infants (48.5%): RSV in 234 (32.4%), RV in 44 (6.1%), hBoV in 11 (1.5%), hMPV in 12 (1.6%), co-infections in 39 (5.4%), and other viruses in 11 (1.5%). Analyzing the 10 epidemic seasons, we found higher incidence for bronchiolitis every 4 years with a peak during the months December-January. Infants hospitalized during peak months had lower family history for asthma (P = 0.003), more smoking mothers during pregnancy (P = 0.036), were slightly higher breastfed (0.056), had lower number of blood eosinophils (P = 0.015) and had a higher clinical severity score (P = 0.017). RSV was detected mostly during peak months, while RV was equally distributed during the seasons. We found some variations in bronchiolitis incidence during epidemics, and discriminative characteristics in infants hospitalized for bronchiolitis during peak months and in non-peak months, that might reflect two different populations of children. Pediatr Pulmonol. 2016;51:1330-1335. © 2016 Wiley Periodicals, Inc.

Lactate dehydrogenase concentration in nasal wash fluid indicates severity of rhinovirus-induced wheezy bronchitis in preschool children.

The clinical course of rhinovirus (RV)-associated wheezing illnesses is difficult to predict. We measured lactate dehydrogenase concentrations, RV load, antiviral and proinflammatory cytokines in nasal washes obtained from 126 preschool children with RV wheezy bronchitis. lactate dehydrogenase values were inversely associated with subsequent need for oxygen therapy. lactate dehydrogenase may be a useful biomarker predicting disease severity in RV wheezy bronchitis.

Seven percent hypertonic saline--0.1% hyaluronic acid in infants with mild-to-moderate bronchiolitis.

OBJECTIVES: Our study was aimed to evaluate the efficacy of 7% hypertonic saline and 0.1% hyaluronic acid (7% HS-HA) given by inhalation, in infants hospitalized for mild-to-moderate bronchiolitis. METHODS: In a double-blind controlled study, 39 infants (23 boys) <7 months of age (median age 2 months) were enrolled and randomly assigned to receive either nebulized 7% HS-HA (7%NaCl + 0.1%HA) (n:21) or 0.9 normal saline (NS) (n:18) at a dose of 2.5 ml twice a day for 3 days. All infants were assigned a clinical severity score at admission and four times daily during hospitalization. Main outcome measures were number of days hospitalization, safety and daily reduction in the severity score. RESULTS: No difference was found between the two groups for clinical severity score at admission. One child in the study group and two in the NS group interrupted the study protocol; 19% of infants in the study group and 11% in the NS group had mild cough after the aerosol. The length of stay in the control group and treatment groups were 4.8 ± 1.5 versus 4.1 ± 1.9 days, respectively (P = 0.09). There was a trend for shortening the hospitalization days in the treatment group by 14.6%. The use of NS in the control group was identified as an independent risk factor for length of hospital stay using the multivariate logistic regression model (P = 0.04). No difference was observed between the two groups for the clinical score reduction during the first 3 days hospitalization. CONCLUSIONS: 7% HS-HA is a safe and effective therapy in treating infants hospitalized for mild-to-moderate bronchiolitis.

Evaluation of viral load in infants hospitalized with bronchiolitis caused by respiratory syncytial virus.

The relationship between viral load, disease severity and antiviral immune activation in infants suffering from respiratory syncytial virus (RSV)-associated bronchiolitis has not been well identified. The main objective of this study was to determine the existence of a correlation between RSV load and disease severity and also between different clinical markers and mRNA levels of the interferon stimulated gene (ISG)56 in infants hospitalized for bronchiolitis. We also evaluated whether viral load tended to be persistent over the course of the RSV infection. The levels of RSV-RNA were quantified in nasopharyngeal washings, collected from 132 infants infected with RSV as a single (90.15%) or as a dual infection with other respiratory viruses (9.85%). Results indicated that viral load was positively related to the clinical severity of bronchiolitis, the length of hospital stay, the levels of glycemia and the relative gene expression of ISG56, whereas an inverse correlation was observed with the levels of hemoglobin. We also found that the RSV load significantly decreased between the first and second nasopharingeal washings sample in most subjects. These results suggest that infants with high RSV load on hospital admission are more likely to have both more severe bronchiolitis and a higher airway activation of antiviral immune response.

Evaluation of interleukin 28B single nucleotide polymorphisms in infants suffering from bronchiolitis.

The genetic diversity of the host is believed to be the key of the diversity in the clinical presentation of bronchiolitis. The aim of this study was to determine whether the known rs12979860 and rs8099917 single nucleotide polymorphisms (SNPs) in interleukin (IL)28B region, influence clinical features and natural history of bronchiolitis. Both SNPs showed no significant association with the risk of hospitalization for respiratory syncytial virus (RSV), viral load, disease severity, and other clinical features of patients. Interestingly infants carrying IL28B rs12979860 TT genotype had lower age at hospital admission than that of infants carrying CC/CT genotypes. Overall our results indicate that both IL28B SNPs had no impact on the clinical course of bronchiolitis with the only exception of the IL28B rs12979860 SNP which increased the risk of hospitalization for bronchiolitis at early age.

What could hemoptysis hide in an otherwise healthy child?

We describe a previously healthy 12-year-old boy who attended our Department after a sudden episode of hemoptysis and recurrent consolidation. CT-scan revealed a mediastinal tumor. The biopsy specimens taken from the mass showed a mature teratoma. Hemoptysis is an unusual presenting symptom in an otherwise healthy child with a well capsulated, unruptured mature mediastinal teratoma. In this report, hemoptysis prompted us to undertake the diagnostic work-up that eventually disclosed the tumor.

Incidence and predisposing factors for severe disease in previously healthy term infants experiencing their first episode of bronchiolitis.

AIM: To determine the incidence and predisposing factors for severe bronchiolitis in previously healthy term infants <12 months of age experiencing their first episode of bronchiolitis. METHODS: Epidemiological, clinical and virological data were prospectively collected. Severity was assessed by the need for ventilatory support. RESULTS: Of the 310 infants enrolled, 16 (5.1%) presented with severe bronchiolitis requiring ventilatory support (11 since admission). Compared with infants with less severe bronchiolitis, infants with severe disease presented with lower birth weight, gestational age, postnatal weight and postnatal age, and were more likely to be born by cesarian section. C-reactive protein positive results (>0.8 mg/dL) and pulmonary consolidation on chest X-ray were more common among infants with severe disease. Severity was independently associated with younger age on admission <30 days, respiratory syncytial virus (RSV) infection and lymphocyte counts < 3200/µL. No significant differences were found between epidemiologic variables. CONCLUSIONS: Severe bronchiolitis is uncommon in previously healthy term infants <12 months of age and when present develops soon after disease onset. Severity is predicted by young age and RSV carriage, whereas epidemiologic variables seem less likely to intervene.

Old and new uses of surfactant.

Exogenous surfactant has been the primary life-saving therapy for respiratory distress syndrome (RDS) of preterm infants for many years. More recently, early surfactant treatment administered less invasively by transient endotracheal intubation and combined to nasal ventilation has been shown to further improve neonatal outcome by reducing the need of mechanical ventilation. In addition to RDS, other neonatal and pediatric respiratory disorders characterized by surfactant inactivation or dysfunction, such as pulmonary hemorrhage, aspiration pneumonia, and viral lower respiratory tract infection, might also be amenable to surfactant replacement therapy. However, the nature of lung injury and the influence of co-morbidities may reduce the efficacy of surfactant in these conditions. Currently under investigation are new synthetic surfactant formulations which may be more effective and resistant to inactivation than natural ones and could be produced at a lower cost. The use of surfactants to deliver drugs directly to the lung also seems to be a promising technique worthy of study.