Occurrence Of Lower Respiratory Tract Infections Research Articles

Asthma occurrence in children and early life systemic antibiotic use: an incidence density study

BackgroundResults of studies evaluating the relationship between asthma occurrence and early life antibiotic use have been conflicting. The aim of this study was to investigate the relationship between occurrence of asthma in children and systemic antibiotic use in the first year of life based on an incidence density study with careful consideration of the temporal aspects of the determinant-outcome relationship.MethodsWe conducted an incidence density study nested in a data collection project with information on 1128 mother–child pairs. Systemic antibiotic use in the first year of life was defined as excessive (≥ 4 courses) vs. non-excessive (< 4 courses) use based on information from weekly diaries. Events (cases) were defined as the first parent-reported occurrence of asthma in a child between 1 and 10 years of age. Population time ‘at risk’ was probed by sampling population moments (controls). Missing data were imputed. Multiple logistic regression was used to assess the association between current first asthma occurrence (incidence density) and systemic antibiotic use in the first year of life, to evaluate effect modification and adjust for confounding.ResultsForty-seven first asthma events and 147 population moments were included. Excessive systemic antibiotic use in the first year of life showed more than twice the incidence density of asthma compared to non-excessive use (adjusted IDR [95% CI]: 2.18 [0.98, 4.87], p = 0.06). The association was more pronounced in children who have had lower respiratory tract infections (LRTIs) in the first year of life compared to children who had no LRTIs in the first year of life (adjusted IDR [95% CI]: 5.17 [1.19, 22.52] versus 1.49 [0.54, 4.14]).ConclusionsExcessive use of systemic antibiotics in the first year of life may play a role in the genesis of asthma in children. This effect is modified by the occurrence of LRTIs in the first year of life, with a stronger association observed in children experiencing LRTIs in the first year of life.

Risk factors for seasonal human coronavirus lower respiratory tract infection after hematopoietic cell transplantation

Data are limited regarding risk factors for lower respiratory tract infection (LRTI) caused by seasonal human coronaviruses (HCoVs) and the significance of virologic documentation by bronchoalveolar lavage (BAL) on outcomes in hematopoietic cell transplant (HCT) recipients. We retrospectively analyzed patients undergoing allogeneic HCT (4/2008-9/2018) with HCoV (OC43/NL63/HKU1/229E) detected by polymerase chain reaction during conditioning or post-HCT. Risk factors for all manifestations of LRTI and progression to LRTI among those presenting with HCoV upper respiratory tract infection (URTI) were analyzed by logistic regression and Cox proportional hazard models, respectively. Mortality rates following HCoV LRTI were compared according to virologic documentation by BAL. A total of 297 patients (61 children and 236 adults) developed HCoV infection as follows: 254 had URTI alone, 18 presented with LRTI, and 25 progressed from URTI to LRTI (median, 16 days; range, 2-62 days). Multivariable logistic regression analyses showed that male sex, higher immunodeficiency scoring index, albumin <3 g/dL, glucose >150 mg/dL, and presence of respiratory copathogens were associated with occurrence of LRTI. Hyperglycemia with steroid use was associated with progression to LRTI (P < .01) in Cox models. LRTI with HCoV detected in BAL was associated with higher mortality than LRTI without documented detection in BAL (P < .01). In conclusion, we identified factors associated with HCoV LRTI, some of which are less commonly appreciated to be risk factors for LRTI with other respiratory viruses in HCT recipients. The association of hyperglycemia with LRTI might provide an intervention opportunity to reduce the risk of LRTI.

1523. Seasonal Human Coronavirus Infections Following Allogeneic Hematopoietic Cell Transplantation: Factors Associated With Lower Respiratory Tract Infection

BackgroundProven/probable lower respiratory tract infection (LRTI) caused by seasonal human coronaviruses (HCoVs) is associated with mortality after hematopoietic cell transplantation (HCT). However, risk factors for LRTI and the significance of virologic documentation of lower respiratory tract involvement by bronchoalveolar lavage (BAL) on outcome are not well characterized.MethodsPatients receiving allogeneic HCT between 4/2008 and 9/2018 with HCoV (OC43/NL63/HKU1/229E) detected in nasopharyngeal or BAL samples by PCR were retrospectively analyzed. Proven/probable LRTI was defined as having virus detected from a BAL sample with or without new pulmonary infiltrates by chest radiography, respectively. Possible LRTI was defined as having virus detected from an upper respiratory tract sample with new pulmonary infiltrates. We used logistic regression models to evaluate risk factors for LRTI in patients with first documented HCoV infection during pretransplant conditioning or post-HCT. Overall mortality following proven/probable and possible LRTI was compared by the log-rank test.ResultsA total of 297 patients (61 children and 236 adults) developed HCoV infection as follows: 254 had upper respiratory tract infection (URTI) alone, 18 presented with LRTI, and 25 progressed from URTI to LRTI [median 16 days (range, 2–62 days)]. Multivariable analyses showed that male gender, higher immunodeficiency scoring index, albumin < 3 g/dl, glucose > 150 mg/dl and presence of respiratory copathogen at HCoV diagnosis were associated with the occurrence of LRTI (Figure 1). Patients with proven/probable LRTI (N=16) had significantly worse survival than those with possible LRTI (N=37) (p=0.006, Figure 2).Figure 1. Figure 2. ConclusionOur analyses identified risk factors (hypoalbuminemia, male gender, high glucose and presence of respiratory copathogen) uncommonly appreciated for LRTI due to other respiratory viruses in HCT recipients. Whether these factors are also relevant to LRTI due to SARS-CoV-2 after HCT requires further studies. The association of hyperglycemia with LRTI might provide an opportunity to reduce the risk of LRTI.Disclosures Alpana Waghmare, MD, Amazon (Grant/Research Support)Amazon (Employee, Shareholder)Ansun Biopharma (Scientific Research Study Investigator)Kyorin Pharmaceuticals (Advisor or Review Panel member) Janet A. Englund, MD, AstraZeneca (Scientific Research Study Investigator)GSK group of companies (Scientific Research Study Investigator)Meissa vaccines (Consultant)Merck (Scientific Research Study Investigator)Sanofi Pasteur (Consultant) Michael Boeckh, MD PhD, AlloVir (Consultant)EvrysBio (Advisor or Review Panel member, Other Financial or Material Support, share options)Gilead (Consultant, Grant/Research Support)GSK (Consultant)Helocyte (Advisor or Review Panel member, Shareholder)Lophius (Grant/Research Support)Merck (Consultant, Grant/Research Support)SymBio (Consultant)VirBio (Consultant, Grant/Research Support)

Study design effect measures for biomass smoke interventions in rural and Native American communities

Introduction. Rural and Native areas of the western United States (US) and Alaska experience substantial exposure and health disparities compared to more populated urban centers. One such source of disparity is the elevated inhalational exposures related to the use of residential wood stoves for home heating. Presented here are detectable effect measures for efficacy testing of indoor air interventions on lower respiratory tract infection (LRTI) in children and pulmonary function in elders. Methods. We designed two, three-arm randomized trials with household level interventions. Indoor air filtration and an education arm focused on best-burning practices were tested against non-intervention arms (placebo). Among children under five in three study areas the primary outcome was incident LRTI. Among elders in two study areas the primary outcome was forced expiratory volume in the first second (FEV1). Results. For the child study we anticipated that robust, active surveillance would yield 16%-44% occurrence of LRTI, depending on the study area. Assuming 80% power and alpha = 0.05, our study design of 162 children per treatment arm (108 homes) yielded a detectable relative risk of 1.46 for the placebo group relative to one of the treatment groups, a relative difference consistent with that observed in similar work. For the elders study our sample size of 42 homes per treatment group allowed for a between group detectable difference in FEV1 of 18.4 ml, or about 50% of mean annual declines typically observed in a general population. Conclusion. These studies currently in progress have substantial power for testing the efficacy of simple, low cost interventions for an important household air pollutant in many rural and Native American communities.

Prenatal exposure to p,p′-DDE and p,p′-DDT in relation to lower respiratory tract infections in boys from a highly exposed area of Mexico

BackgroundPrenatal exposure to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p′-DDE), the major breakdown product of DDT, has been associated with recurrent lower respiratory tract infections (LRTIs) in infants. However, epidemiological investigations are limited. ObjectiveTo assess the association of prenatal exposure to p,p′-DDE and p,p′-DDT with the occurrence of LRTI in boys from Chiapas, a highly exposed area of Mexico. MethodsWe analyzed data from 747 singleton boys whose prenatal exposure to p,p′-DDE and p,p′-DDT was determined in maternal serum drawn at delivery (2002–2003). LRTI (i.e., pneumonia, bronchiolitis, and other illness of the bronchi) experienced by the children were reported by their mothers during in-person interviews. The median age of the children when they were last seen was 21.4 months (quartiles 19.1 and 25.3 months). ResultsMedian exposure to p,p′-DDE in this population was higher (2.7µg/g lipid) than recent U.S. levels (0.20µg/g). There were 0.19 episodes of LRTI per child-year. After adjusting for potential confounders, children in the highest category of p,p′-DDE (>9.00µg/g) exposure compared to those in the lowest (≤3.00µg/g) had an adjusted incidence rate ratio (aIRR) of LRTI of 0.77 (95% confidence interval [CI], 0.41–1.46). The corresponding aIRR for p,p′-DDT (≥2.00µg/g compared to ≤0.25µg/g) was 0.65 (95% CI: 0.30–1.39). ConclusionAn association of prenatal exposure to p,p′-DDE and p,p′-DDT with LRTI during childhood was not supported in this population with relatively high levels of exposure.

Formaldehyde Exposure and Lower Respiratory Infections in Infants: Findings from the PARIS Cohort Study

Background: Certain chemical pollutants can exacerbate lower respiratory tract infections (LRIs), a common childhood ailment. Although formaldehyde (FA) is one of the most common air pollutants found in indoor environments, its impact on infant health is uncertain.Objective: Our aim was to determine the impact of FA exposure on the LRI incidence during the first year of life of infants from the Pollution and Asthma Risk: an Infant Study (PARIS) birth cohort.Methods: FA was measured in a random sample of 196 infants’ dwellings, and exposure to this pollutant was estimated for 2,940 infants using predictive models based on measurements and data about potential determinants of FA levels. Health data were collected from parents by regular self-administered questionnaires. We used multivariate logistic regressions to estimate associations between FA exposure and the occurrence of LRI and wheezy LRI (wLRI), adjusting for potential confounders/risk factors.Results: During the first year of life, 45.8% of infants had at least one LRI, and LRI occurred simultaneously with wheezing in 48.7% of cases. The FA predictive models correctly classified 70% of dwellings as having high or low exposure, and we estimated that 43.3% of infants were exposed throughout the first year to levels of FA > 19.5 µg/m3. FA exposure was significantly associated with LRI and wLRI before and after adjustment for known LRI risk factors/confounders. For an interquartile increase in FA levels (12.4 μg/m3), we estimated a 32% [95% confidence interval (CI): 11, 55] and 41% (95% CI: 14, 74) increase in the incidence of LRI and wLRI, respectively.Conclusion: The findings of this study suggest that infants exposed to FA at an early age have an increased incidence of LRI.

Lower respiratory tract respiratory virus infections increase the risk of invasive aspergillosis after a reduced-intensity allogeneic hematopoietic SCT

We have analyzed the incidence and risk factors for the occurrence of invasive aspergillosis (IA) among 219 consecutive recipients of an allogeneic hematopoietic SCT after a reduced-intensity conditioning regimen (Allo-RIC). Twenty-seven patients developed an IA at a median of 218 days (range 24–2051) post-Allo-RIC, for a 4-year incidence of 13% (95% confidence interval 4–24%). In multivariate analysis, risk factors for developing IA were steroid therapy for moderate-to-severe graft vs host disease (GVHD) (Hazard Ratio (HR) 2.9, P=0.03), occurrence of a lower respiratory tract infection (LRTI) by a respiratory virus (RV) (HR 4.3, P<0.01) and CMV disease (HR 2.8, P=0.03). Variables that decreased survival after Allo-RIC were advanced disease phase (HR 1.9, P=0.02), steroid therapy for moderate-to-severe GVHD (HR 2.2, P<0.01), not developing chronic GVHD (HR 4.3, P<0.01), occurrence of LRTI by an RV (HR 3.4, P<0.01) and CMV disease (HR 2, P=0.01), whereas occurrence of IA had no effect on survival (P=0.5). Our results show that IA is a common infectious complication after an Allo-RIC, which occurs late post-transplant and may not have a strong effect on survival. An important observation is the possible role of LRTI by conventional RVs as risk factors for IA.

Acute viral lower respiratory tract infections in children

Viruses are the most common cause of lower respiratory tract infections (LRTIs) in infants and young children and are a major public health problem in this age group. Viruses were identified in 54.9-70.4% of hospitalized infants and children with LRTIs in Korea. The viral pathogens identified included respiratory syncytial virus (RSV) A and RSV B, influenza (Inf) A, Inf B, parainfluenza (PIV)1, PIV2, human bocavirus (hBoV), human rhinovirus (hRV), adenovirus (ADV), human metapneumovirus (hMPV), human coronavirus (hCoV)-OC 43, hCoV-229E, hCoV-NL63, hCoV-HKU1, and human enterovirus (hEV). Coinfections with 2 viruses were observed in 11.5-22.8% of children. The occurrence of LRTIs was the highest in the first year of life. The specific viruses are frequently associated with specific clinical syndromes of LRTIs. LRTIs caused by RSV were predominant among younger infants. hRV accounted for a larger proportion of LRTIs in young infants than ADV and hBoV. hMPV was frequently detected in children >24 months old. The number of hMPV infections peaked between February and May, whereas hRV was detected throughout the year. Thus far, hCoV is a less common respiratory pathogen in cases of ALRI and URI in Korean children.