Respiratory viruses in healthy infants and infants with cystic fibrosis: a prospective cohort study

Korten, Insa; Kieninger, Elisabeth; Klenja, Shkipe; Mack, Ines; Schläpfer, Njima; Barbani, Maria Teresa; Regamey, Nicolas; Kuehni, Claudia E.; Hilty, Markus; Frey, Urs; Gorgievski, Meri; Casaulta, Carmen; Latzin, Philipp; Scild,; groups, Bild study

doi:10.1136/thoraxjnl-2016-209553

Cited by 15 publications

(11 citation statements)

References 41 publications

(10 reference statements)

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“…Prior studies in healthy infants show a wide range of viral positivity, anywhere from 23% [ 23 ] to 69% [ 19 ]. Comparing to studies examining viruses in the first year of life [ 19 , 20 , 22 , 24 ], we found comparable findings as in those studies viral positivity ranged from 27% [ 24 ] to 69% [ 19 ] in healthy infants. Our rates of detection in home versus clinic collected samples were not significantly different.…”

Section: Discussionsupporting

confidence: 86%

“…Lastly, we did not have a control group due to the nature of the study protocol which included bronchoscopy and infant lung function testing, sedated procedures that would not be electively performed on healthy infants. However, there are multiple epidemiologic studies of viral infections in healthy infants to which our prevalence results are comparable [ 19 , 20 , 22 , 24 ].…”

Section: Discussionmentioning

confidence: 80%

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Early respiratory viral infections in infants with cystic fibrosis

Deschamp

Hatch

Slaven

et al. 2019

Journal of Cystic Fibrosis

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a b s t r a c tBackground: Viral infections contribute to morbidity in cystic fibrosis (CF), but the impact of respiratory viruses on the development of airway disease is poorly understood. Methods: Infants with CF identified by newborn screening were enrolled prior to 4 months of age to participate in a prospective observational study at 4 centers. Clinical data were collected at clinic visits and weekly phone calls. Multiplex PCR assays were performed on nasopharyngeal swabs to detect respiratory viruses during routine visits and when symptomatic. Participants underwent bronchoscopy with bronchoalveolar lavage (BAL) and a subset underwent pulmonary function testing. We present findings through 8.5 months of life. Results: Seventy infants were enrolled, mean age 3.1 ± 0.8 months. Rhinovirus was the most prevalent virus (66%), followed by parainfluenza (19%), and coronavirus (16%). Participants had a median of 1.5 viral positive swabs (range 0-10). Past viral infection was associated with elevated neutrophil concentrations and bacterial isolates in BAL fluid, including recovery of classic CF bacterial pathogens. When antibiotics were prescribed for respiratory-related indications, viruses were identified in 52% of those instances. Conclusions: Early viral infections were associated with greater neutrophilic inflammation and bacterial pathogens. Early viral infections appear to contribute to initiation of lower airway inflammation in infants with CF. Antibiotics were commonly prescribed in the setting of a viral infection. Future investigations examining longitudinal relationships between viral infections, airway microbiome, and antibiotic use will allow us to elucidate the interplay between these factors in young children with CF.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 80%

Early respiratory viral infections in infants with cystic fibrosis

Deschamp

Hatch

Slaven

et al. 2019

Journal of Cystic Fibrosis

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“…The prevalence of respiratory virus in this study was 35.7%. In agreement with previous studies, picornaviridae viruses were the most frequently detected viruses, regardless of age [ 4 – 9 , 12 , 20 , 21 ]. RSV was the second most frequent virus, and had the lowest hospital admission rate, even though it has been suggested that CF patients could be at risk for more severe infection by this agent [ 22 ].…”

Section: Discussionsupporting

confidence: 92%

Clinical impact of respiratory virus in pulmonary exacerbations of children with Cystic Fibrosis

et al. 2020

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Backgrounds Cystic Fibrosis (CF) is a genetic, multisystemic, progressive illness that causes chronic suppurative lung disease. A major cause of morbimortality in this condition are pulmonary exacerbations. Although classically attributed to bacterial infections, respiratory virus have been increasingly recognized in its ethiopathogeny. Methods Nasopharyngeal swab samples were collected from children < 18 years old with CF in Rio de Janeiro, Brazil, with pulmonary exacerbation criteria. Samples were submitted to RT-PCR for Adenovirus, Influenza A and B, Parainfluenza Virus, Respiratory Syncytial Virus (RSV), Metapneumovirus and Rhinovirus. Virus positive and virus negative groups were compared in regards to clinical presentation, severity of exacerbation and bacterial colonization. Results Out of 70 samples collected from 48 patients, 35.7% were positive for respiratory viruses. Rhinovirus were the most common (28% of all positive samples), followed by RSV. The virus positive group was associated with change in sinus discharge (p = 0.03). Considering only patients younger than five years old, positive virus detection was also associated with fever (p = 0.01). There was no significant difference in clinical severity or in bacterial colonization between virus positive and negative groups. Conclusions Prospective studies are still needed to assess the long term impact of viral infections in patients with CF, and their interaction with the bacterial microbiome in these patients.

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“…does not impact airway neutrophil CD63 expression at the time of the measurement, we cannot exclude potential impact of prior infections, or low-level presence of atypical organisms (24). Viral infections may also be at play, although a recent study suggested that children with CF do not suffer more frequent viral infections or increased inflammatory responses on viral infections than children without CF (64).…”

Section: Discussionmentioning

confidence: 89%

Elastase Exocytosis by Airway Neutrophils Is Associated with Early Lung Damage in Children with Cystic Fibrosis

Margaroli

Garratt

Horati

et al. 2019

Am J Respir Crit Care Med

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Rationale: Neutrophils are recruited to the airways of individuals with cystic fibrosis (CF). In adolescents and adults with CF, airway neutrophils actively exocytose the primary granule protease elastase (NE), whose extracellular activity correlates with lung damage. During childhood, free extracellular NE activity is measurable only in a subset of patients, and the exocytic function of airway neutrophils is unknown.Objectives: To measure NE exocytosis by airway neutrophils in relation to free extracellular NE activity and lung damage in children with CF.Methods: We measured lung damage using chest computed tomography coupled with the Perth-Rotterdam Annotated Grid Morphometric Analysis for Cystic Fibrosis scoring system. Concomitantly, we phenotyped blood and BAL fluid leukocytes by flow and image cytometry, and measured free extracellular NE activity using spectrophotometric and Förster resonance energy transfer assays. Children with airway inflammation linked to aerodigestive disorder were enrolled as control subjects.Measurements and Main Results: Children with CF but not disease control children harbored BAL fluid neutrophils with high exocytosis of primary granules, before the detection of bronchiectasis. This measure of NE exocytosis correlated with lung damage (R = 0.55; P = 0.0008), whereas the molecular measure of free extracellular NE activity did not. This discrepancy may be caused by the inhibition of extracellular NE by BAL fluid antiproteases and its binding to leukocytes.Conclusions: NE exocytosis by airway neutrophils occurs in all children with CF, and its cellular measure correlates with early lung damage. These findings implicate live airway neutrophils in early CF pathogenesis, which should instruct biomarker development and antiinflammatory therapy in children with CF.

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Respiratory viruses in healthy infants and infants with cystic fibrosis: a prospective cohort study

Cited by 15 publications

References 41 publications

Early respiratory viral infections in infants with cystic fibrosis

Early respiratory viral infections in infants with cystic fibrosis

Clinical impact of respiratory virus in pulmonary exacerbations of children with Cystic Fibrosis

Elastase Exocytosis by Airway Neutrophils Is Associated with Early Lung Damage in Children with Cystic Fibrosis

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