Impact Of Respiratory Tract Infections Research Articles

A Multicenter, Longitudinal Maternal and Birth Cohort Study in Latin America to Assess Prevalent Respiratory Tract Infections in Children from 0 to 5 Years of Age. The MINERVAL Study

Abstract Background A maternal and birth cohort study can assess the etiology and clinical course of lower respiratory tract infections and offers the opportunity to evaluate the relationship between sociodemographic, clinical, host characteristics and disease severity. In Latin America, a consortium of clinical research centers in Colombia and Panama has demonstrated its ability to conduct long-term longitudinal studies involving active surveillance of thousands of children with consistent retention rates. The MINERVAL cohort study aims to estimate the incidence, etiology, severity, and burden of lower respiratory tract infections (LRTI) and to identify microbiome and transcriptome profiles to help predict risk and assess disease severity in children from birth to 5 years of age. Methods We are establishing a maternal/birth cohort study in four sites (Cali, Bogota, Barranquilla and Panama), and will be recruiting 542 participants per center. Enrolled pregnant women between 24 and 27 weeks of gestation, and newborns under 4 weeks of age, will be closely followed with active surveillance weekly during the first 2 years for early detection of LRTI. Monthly telephone follow-up calls will continue until five years of age to assess the development of long-term respiratory morbidity and complications, including recurrent wheezing episodes. Clinical samples (NP swabs -for respiratory pathogen detection and microbiome analysis-, and blood -for cytokine and transcriptome analysis-) will be obtained in pregnant women, and in infants in the first 4 weeks of life and every 6 months for two years. Women and children who develop LRTI during the longitudinal follow-up will be evaluated clinically and samples will be collected. Results This cohort will provide prospective data and biological samples at crucial stages of children’s development, to allow estimation of the incidence and burden of LRTI by age and etiology, and the identification of risk factors and possible targets for intervention. Furthermore, the use of transcriptional profiling will allow early identification of variables to predict and guide clinical management in children, the use of antivirals and monoclonal antibodies, and to prioritize the population to be vaccinated according to age and risk factors. Conclusion The establishment of observational maternal and birth cohorts in Latin America could provide information to guide the development of strategies to prevent and mitigate the impact of respiratory tract infections in young children. Collaboration among investigators in the region and partnerships with international investigators optimizes resources and allows standardization of good surveillance practices, data exchange and the generation of new knowledge for future studies.

Impact of respiratory tract infections on spinal muscular atrophy with focus on respiratory syncytial virus infections: a single-centre cohort study.

Spinal muscular atrophy (SMA) is a degenerative neuromuscular disorder leading to muscle hypotonia, weakness, and respiratory and bulbar impairment. Infants with SMA have an increased risk of respiratory tract infections (RTI) including severe respiratory syncytial virus (RSV) infections. Therefore, guidelines for the treatment of SMA recommend RSV prophylaxis with palivizumab for patients aged below two years who have compromised motor functions ("non-sitters"). Since palivizumab is not approved for RSV prophylaxis in SMA patients in Switzerland, payers usually do not grant cost approvals for this indication. Therefore, this study aimed to investigate the frequency of severe RTI among SMA patients focusing on RSV infections requiring hospital treatment and to determine the long-term impact of RSV infections on the natural history of SMA. A single-centre cohort study at the tertiary paediatric Neuromuscular Centre Zurich, Switzerland, including data of SMA patients with a genetic-based therapy initiated below two years of age between May 2019 and December 2022. All hospitalisations were analysed with a focus on severe RTI and especially RSV infections, and their impact on nutritional and respiratory function. The costs of inpatient treatment of RSV infections were determined and compared with estimated expenses for RSV prophylaxis with palivizumab. 12 SMA patients (median age at treatment initiation: 3.5 months, range: 0-17 months) were followed for a cumulative period of 25.75 years (7 SMA type 1; 5 SMA type 2 including one presymptomatic individual). With an incidence rate of 2.34 per patient-year, the risk of severe RTI was especially high in SMA type 1 (versus 0.1 in SMA type 2, p = 0.044). A total of 37 hospitalisations (279 hospital days) was necessary for the treatment of RTI in general; 9 of them were attributed to RSV infections (in 5 SMA type 1 patients; 84 hospital days). Only 3/12 SMA patients had received seasonal RSV prophylaxis with palivizumab. No RSV infections requiring hospital treatment occurred in patients while receiving seasonal RSV prophylaxis. During RTI, nutritional support had to be commonly initiated and continued after discharge. In 3/7 SMA type 1 patients, non-invasive ventilation was started during acute treatment for RTI and continued to the end of follow-up. We observed a high risk of RTI, especially RSV infections, among young SMA patients. Failure to adhere to established care protocols, for example by omitting RSV prophylaxis, may be linked to a heightened risk of morbidity in these children.

Infant nasal nitric oxide over time: natural evolution and impact of respiratory tract infection.

Nasal nitric oxide (NO) discriminates between patients with primary ciliary dyskinesia (PCD) and healthy individuals. We report feasibility of measurement and natural evolution of nasal NO and upon the impact of respiratory tract infection (RTI) on nasal NO in healthy infants (HI), followed from birth until age 2 years, with comparison to nasal NO in infant PCD.Tidal-breathing nasal NO measurements were performed at scheduled visits at 2 weeks old and at 4, 8, 12, 18 and 24 months old, with extra visits during RTIs. Historical nasal NO measurements for infant PCD were included for comparison.Altogether, 224 nasal NO measurements were performed in 44 enrolled infants. Median newborn nasal NO was 46 ppb (interquartile range (IQR) 29-69 ppb), increasing at a rate of 5.4% per month up to 283 ppb (IQR 203-389 ppb) at the age of 2 years. RTIs in 27 out of 44 infants temporarily suppressed nasal NO by 79%. Values for nasal NO in seven infants with PCD ranged from 6-80 ppb. The success rate to accept nasal NO sampling was 223 out of 224 measurements (99.6%).Tidal-breathing nasal NO measurement was indeed feasible in infancy and nasal NO in HI increased significantly up to 2 years of age, in opposition to nasal NO in PCD cases, which stayed low past 2 years of age. RTI episodes caused marked, temporary reductions in nasal NO in HI indistinguishable from that in infant PCD, suggesting that nasal NO should be measured in RTI-free intervals.

Post-operative kinetics of procalcitonin after lung transplantation

Post-operative infections are a major complication after lung transplantation (LT). Early bacterial pneumonia worsens the prognosis of LT. Procalcitonin (PCT) has been proposed as an early and rapid laboratory marker of infection and sepsis. PCT could be a useful biomarker of pulmonary infection after LT, but the early kinetics of PCT in this setting are unknown. We evaluated the kinetics of PCT and the impact of respiratory tract infection on PCT concentrations. Over a 12-month period, PCT concentrations were determined daily in each patient admitted to our ICU for LT. Epidemiologic, clinical, laboratory and outcome data were obtained. A diagnosis of respiratory tract infection was suspected on clinical examination and confirmed by microbiologic culture. Twenty-six consecutive patients were included and 397 blood samples were obtained (13 [range 4 to 66] samples per patient). Plasma PCT reached a peak in the first 24 hours post-transplantation (5.72 [0.11 to 93.8] ng/ml), with a progressive decline over the first 7 post-operative days. Doubling of plasma PCT levels after an initial decrease was significantly associated with respiratory tract infection in transplanted patients (RR = 4.2 95% CI [1.95 to 9.03]). A non-specific increase in PCT values was observed during the first week post-LT. In combination with microbiologic cultures, PCT assays may be useful after the first post-operative week as an aid in the diagnosis of bacterial pulmonary infection.

Impact of Respiratory Tract Infections on Developmental Skills in Children With Down Syndrome

Background and aims: Recurrent respiratory tract infections (RRTI) have a significant impact on the developmental age of children with Down Syndrome (DS). Since RRTI are related to impaired hearing we proposed that verbal skills are more influenced compared to perceptual-performance, quantitative, memory and motor development in these children. Methods: During a 3-year period, all members of the Dutch DS Foundation with an 8-year-old child with DS were asked to participate in this study. If parents agreed, a psychological assistant administrated the McCarthy Scales of Children's Abilities. Based on parental report, the children were divided into increased RRTI (RRTI+) and no increased RRTI (RRTI-). Linear regression analyses were performed to assess the effect of RRTI on the outcomes and the interaction with impaired hearing, adjusted for confounders. Results: Compared to RRTI- children (n=176; missing data n=12), RRTI+ children (n=149, 46%) showed lower mean developmental age (3.67 vs. 4.08 years). Impaired hearing was more common in RRTI+ (44% vs 18%, p-values< 0.001). RRTI+ children had lower scores on all scales (verbal, perceptual-performance, quantitative, memory and motor development; p-values < .001) with equal effect sizes (f2=.03-.04). Interaction with impaired hearing was not observed. Conclusions: RRTI are related to delayed development in 8-year-old DS children. Although hearing loss is a common problem in RRTI+ children with DS, it does not lead to a more profound decrease in verbal skills compared to other domains of development. Since RRTI are potentially preventable, further studies should focus on causes and improved treatment of RRTI in children with DS.

Developmental alterations in auditory arousal from sleep in healthy and virus-infected cats.

To investigate the impact of respiratory-tract infections on arousability from sleep, we evaluated the auditory arousal responses of healthy and virus-infected cats in two age groups. Arousability was positively associated with stimulus intensity but negatively associated with experimental day. Infected animals were more responsive to auditory stimuli than were uninfected ones, and younger cats were less responsive than older animals. Within the younger groups, infected cats demonstrated increased arousability across the entire range of stimulus volumes during quiet sleep but not during active sleep. Young infected cats also demonstrated lower EEG delta-wave amplitudes than did uninfected animals. These effects on arousability and EEG amplitudes were not observed in older cats. Thus, under the conditions studied, cats with mild viral infections show an age-related enhancement of auditory arousability from sleep, suggesting that they sleep less deeply than do healthy, age-matched animals. The generalization of these observations to other arousing stimuli, such as hypoxia or hypercapnia, and possible implications for the pathogenesis of sudden infant death syndrome remain to be determined.

Economic costs of respiratory tract infections in the United States

To evaluate one aspect of the impact of respiratory tract infections in the United States, national survey data were used to estimate direct and indirect economic costs. Overall, upper and lower respiratory tract infections are estimated to be responsible for approximately $15 billion in direct treatment costs. Physician charges account for about one half and hospital care accounts for approximately one quarter of these costs. An estimated 1.25 million patients are hospitalized yearly for community-acquired respiratory tract infections, and charges for their care are projected to exceed $4 billion. Almost 300 thousand patients acquire nosocomial respiratory infections yearly, and charges for treating these infections are approximately $470 million. Although costs associated with hospital care are substantial, approximately $10 billion (67 percent of the total estimated cost of these infections) results from treatment of patients In ambulatory settings. It Is not possible to calculate the full magnitude of the indirect costs of respiratory infections, but losses in income of employed persons who miss work because of Infection are calculated to be more than $9 billion per year.