Browsing by Author "Ranganathan, Sarath"

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    Association between early respiratory viral infections and structural lung disease in infants with cystic fibrosis
    (Elsevier, 2022) Sanders, Don B.; Deschamp, Ashley R.; Hatch, Joseph E.; Slaven, James E.; Gebregziabher, Netsanet; Kemner-van de Corput, Mariette; Tiddens, Harm A. W. M.; Rosenow, Tim; Storch, Gregory A.; Hall, Graham L.; Stick, Stephen M.; Ranganathan, Sarath; Ferkol, Thomas W.; Davis, Stephanie D.; Pediatrics, School of Medicine
    Background: Infants with cystic fibrosis (CF) develop structural lung disease early in life, and viral infections are associated with progressive lung disease. We hypothesized that the presence of respiratory viruses would be associated with structural lung disease on computed tomography (CT) of the chest in infants with CF. Methods: Infants with CF were enrolled before 4 months of age. Multiplex PCR assays were performed on nasal swabs to detect respiratory viruses during routine visits and when symptomatic. Participants underwent CT imaging at approximately 12 months of age. Associations between Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF) CT scores and respiratory viruses and symptoms were assessed with Spearman correlation coefficients. Results: Sixty infants were included for analysis. Human rhinovirus was the most common virus detected, on 28% of tested nasal swabs and in 85% of participants. The median (IQR) extent of lung fields that was healthy based on PRAGMA-CF was 98.7 (0.8)%. There were no associations between PRAGMA-CF and age at first virus, or detection of any virus, including rhinovirus, respiratory syncytial virus, or parainfluenza. The extent of airway wall thickening was associated with ever having wheezed (ρ = 0.31, p = 0.02) and number of encounters with cough (ρ = 0.25, p = 0.0495). Conclusions: Infants with CF had minimal structural lung disease. We did not find an association between respiratory viruses and CT abnormalities. Wheezing and frequency of cough were associated with early structural changes.
  • Thumbnail Image
    Item
    Association between early respiratory viral infections and structural lung disease in infants with cystic fibrosis
    (Elsevier, 2022-11) Sander, Don B.; Deschamp, Ashley R.; Hatch, Joseph E.; Slaven, James E.; Gebregziabher, Netsanet; Kemner-van de Corput, Mariette; Tiddens, Harm A. W. M.; Rosenow, Tim; Storch, Gregory A.; Hall, Graham L.; Stick, Stephen M.; Ranganathan, Sarath; Ferkol, Thomas W.; Davis, Stephanie D.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Background: Infants with cystic fibrosis (CF) develop structural lung disease early in life, and viral infections are associated with progressive lung disease. We hypothesized that the presence of respiratory viruses would be associated with structural lung disease on computed tomography (CT) of the chest in infants with CF. Methods: Infants with CF were enrolled before 4 months of age. Multiplex PCR assays were performed on nasal swabs to detect respiratory viruses during routine visits and when symptomatic. Participants underwent CT imaging at approximately 12 months of age. Associations between Perth-Rotterdam Annotated Grid Morphometric Analysis for CF (PRAGMA-CF) CT scores and respiratory viruses and symptoms were assessed with Spearman correlation coefficients. Results: Sixty infants were included for analysis. Human rhinovirus was the most common virus detected, on 28% of tested nasal swabs and in 85% of participants. The median (IQR) extent of lung fields that was healthy based on PRAGMA-CF was 98.7 (0.8)%. There were no associations between PRAGMA-CF and age at first virus, or detection of any virus, including rhinovirus, respiratory syncytial virus, or parainfluenza. The extent of airway wall thickening was associated with ever having wheezed (ρ = 0.31, p = 0.02) and number of encounters with cough (ρ = 0.25, p = 0.0495). Conclusions: Infants with CF had minimal structural lung disease. We did not find an association between respiratory viruses and CT abnormalities. Wheezing and frequency of cough were associated with early structural changes.
  • Thumbnail Image
    Item
    Association of Antibiotics, Airway Microbiome, and Inflammation in Infants with Cystic Fibrosis
    (American Thoracic Society, 2017-10) Pittman, Jessica E.; Wylie, Kristine M.; Akers, Kathryn; Storch, Gregory A.; Hatch, Joseph; Quante, Jane; Frayman, Katherine B.; Clarke, Nadeene; Davis, Miriam; Stick, Stephen M.; Hall, Graham L.; Montgomery, Gregory; Ranganathan, Sarath; Davis, Stephanie D.; Ferkol, Thomas W.; Pediatrics, School of Medicine
    RATIONALE: The underlying defect in the cystic fibrosis (CF) airway leads to defective mucociliary clearance and impaired bacterial killing, resulting in endobronchial infection and inflammation that contributes to progressive lung disease. Little is known about the respiratory microbiota in the early CF airway and its relationship to inflammation. OBJECTIVES: To examine the bacterial microbiota and inflammatory profiles in bronchoalveolar lavage fluid and oropharyngeal secretions in infants with CF. METHODS: Infants with CF from U.S. and Australian centers were enrolled in a prospective, observational study examining the bacterial microbiota and inflammatory profiles of the respiratory tract. Bacterial diversity and density (load) were measured. Lavage samples were analyzed for inflammatory markers (interleukin 8, unbound neutrophil elastase, and absolute neutrophil count) in the epithelial lining fluid. RESULTS: Thirty-two infants (mean age, 4.7 months) underwent bronchoalveolar lavage and oropharyngeal sampling. Shannon diversity strongly correlated between upper and lower airway samples from a given subject, although community compositions differed. Microbial diversity was lower in younger subjects and in those receiving daily antistaphylococcal antibiotic prophylaxis. In lavage samples, reduced diversity correlated with lower interleukin 8 concentration and absolute neutrophil count. CONCLUSIONS: In infants with CF, reduced bacterial diversity in the upper and lower airways was strongly associated with the use of prophylactic antibiotics and younger age at the time of sampling; less diversity in the lower airway correlated with lower inflammation on bronchoalveolar lavage. Our findings suggest modification of the respiratory microbiome in infants with CF may influence airway inflammation.
  • Thumbnail Image
    Item
    The clinical utility of lung clearance index in early cystic fibrosis lung disease is not impacted by the number of multiple-breath washout trials
    (European Respiratory Society, 2018-02-16) Foong, Rachel E.; Harper, Alana J.; Skoric, Billy; King, Louise; Turkovic, Lidija; Davis, Miriam; Clem, Charles C.; Rosenow, Tim; Davis, Stephanie D.; Ranganathan, Sarath; Hall, Graham L.; Ramsey, Kathryn A.; Pediatrics, School of Medicine
    The lung clearance index (LCI) from the multiple-breath washout (MBW) test is a promising surveillance tool for pre-school children with cystic fibrosis (CF). Current guidelines for MBW testing recommend that three acceptable trials are required. However, success rates to achieve these criteria are low in children aged <7 years and feasibility may improve with modified pre-school criteria that accepts tests with two acceptable trials. This study aimed to determine if relationships between LCI and clinical outcomes of CF lung disease differ when only two acceptable MBW trials are assessed. Healthy children and children with CF aged 3-6 years were recruited for MBW testing. Children with CF also underwent bronchoalveolar lavage fluid collection and a chest computed tomography scan. MBW feasibility increased from 46% to 75% when tests with two trials were deemed acceptable compared with tests where three acceptable trials were required. Relationships between MBW outcomes and markers of pulmonary inflammation, infection and structural lung disease were not different between tests with three acceptable trials compared with tests with two acceptable trials. This study indicates that pre-school MBW data from two acceptable trials may provide sufficient information on ventilation distribution if three acceptable trials are not possible.
  • Thumbnail Image
    Item
    Early respiratory viral infections in infants with cystic fibrosis
    (Elsevier, 2019-11) Deschamp, Ashley R.; Hatch, Joseph E.; Slaven, James E.; Gebregziabher, Netsanet; Storch, Gregory; Hall, Graham L.; Stick, Stephen; Ranganathan, Sarath; Ferkol, Thomas W.; Davis, Stephanie D.; Biostatistics, School of Public Health
    Background 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.
  • Thumbnail Image
    Item
    Hyperinflation is Associated with Increased Respiratory Rate and is a More Sensitive Measure of Cystic Fibrosis Lung Disease During Infancy Compared to Forced Expiratory Measures
    (Wiley, 2021-09) Muston, Heather N.; Slaven, James E.; Tiller, Christina; Clem, Charles; Ferkol, Thomas W.; Ranganathan, Sarath; Davis, Stephanie D.; Ren, Clement L.; Pediatrics, School of Medicine
    Background The goal of this study was to identify clinical features associated with abnormal infant pulmonary function tests (iPFTs), specifically functional residual capacity (FRC), in infants with cystic fibrosis (CF) diagnosed via newborn screen (NBS). We hypothesized that poor nutritional status in the first 6-12 months would be associated with increased FRC at 12-24 months. Methods This study utilized a combination of retrospectively and prospectively collected data from ongoing research studies and iPFTs performed for clinical indications. Demographic and clinical features were obtained from the electronic medical record. Forced expiratory flows and volumes were obtained using the raised volume rapid thoracoabdominal technique (RVRTC) and FRC was measured via plethysmography. Results A total of 45 CF NBS infants had iPFTs performed between 12-24 months. Mean forced vital capacity, forced expiratory volume in 0.5 second, and forced expiratory flows were all within normal limits. In contrast, the mean FRC z-score was 2.18 (95%CI=1.48, 2.88) and the mean respiratory rate (RR) z-score was 1.42 (95%CI=0.95, 1.89). There was no significant association between poor nutritional status and abnormal lung function. However, there was a significant association between higher RR and increased FRC, and a RR cutoff of 36 breaths/min resulted in 92% sensitivity to detect hyperinflation with 32% specificity. Conclusions These results suggest that FRC is a more sensitive measure of early CF lung disease than RVRTC measurements and that RR may be a simple, non-invasive clinical marker to identify CF NBS infants with hyperinflation. This article is protected by copyright. All rights reserved.