title: An observational study examining the relationship between respiratory symptoms, airway inflammation and bacteriology in children with severe neurodisability.
abstract: BACKGROUND
  Children with severe neurodisability (ND) commonly suffer from chronic respiratory symptoms that impact greatly on quality of life, and lead to recurrent hospital admissions. This morbidity (and its causes) is poorly described, despite being well recognised by paediatricians. In this study, we characterised respiratory symptoms in children with ND at times of stability and deterioration. We also assessed the relationship between respiratory symptoms, lower airway inflammatory markers and levels of infection/colonisation.
  
  
  METHODS
  ND children were recruited upon admission for elective surgery (Elective-ND [n = 16]), or acutely upon admission to Intensive Care (PICU-ND [n = 19]), and compared to healthy control children [n = 12]. Parents completed a validated respiratory symptom questionnaire in which symptoms associated with activity were removed (total maximal score of 108). Bronchoalveolar lavage (BAL) was collected, and BAL neutrophil counts, IL-8 and TGFβ-1 levels measured. BAL microbial analysis was performed using a 16S/18S rRNA gene based assay and Pseudomonas aeruginosa PCR.
  
  
  RESULTS
  All ND children had high levels of respiratory symptoms (median [IQR] symptom score PICU-ND, 55[38-64]; Elective-ND, 26[7-45]; Control, 4[0-7]: p<0.01), which affected their families, particularly at nighttime. Elective-ND patients with a total respiratory symptom score >20 invariably had BAL neutrophilia. Elective patients with 16S/18S microbial rDNA positive BAL had higher neutrophil counts (positive, 33[18-70]%; negative, 8[4-38]%: p<0.05) and generally higher symptom scores (positive, 17[5-32]; negative, 5[0-9]: p = 0.097). Streptococcus mitis was commonly identified in BAL from ND children; Pseudomonas aeruginosa was not identified in any sample.
  
  
  CONCLUSIONS
  Children with severe ND often have high levels of chronic respiratory symptoms, which may relate to lower airway inflammation. Bacterial airway colonisation, particularly with oral commensals, may play a role in both symptom generation and inflammation.
authors: Alder Hey Children's Hospital NHS Foundation Trust, Eaton Rd, Liverpool, United Kingdom; Institute of Translational Medicine (Child Health), University of Liverpool, Alder Hey Children's Hospital, Eaton Road, Liverpool, United Kingdom.
authors: Ruth E
authors: RE
authors: Trinick
authors: Institute of Translational Medicine (Child Health), University of Liverpool, Alder Hey Children's Hospital, Eaton Road, Liverpool, United Kingdom.
authors: Lara
authors: L
authors: Bunni
authors: Alder Hey Children's Hospital NHS Foundation Trust, Eaton Rd, Liverpool, United Kingdom.
authors: Kent
authors: K
authors: Thorburn
authors: Institute of Translational Medicine (Child Health), University of Liverpool, Alder Hey Children's Hospital, Eaton Road, Liverpool, United Kingdom.
authors: Angela P
authors: AP
authors: Hackett
authors: Alder Hey Children's Hospital NHS Foundation Trust, Eaton Rd, Liverpool, United Kingdom.
authors: Mark
authors: M
authors: Dalzell
authors: Alder Hey Children's Hospital NHS Foundation Trust, Eaton Rd, Liverpool, United Kingdom; Institute of Translational Medicine (Child Health), University of Liverpool, Alder Hey Children's Hospital, Eaton Road, Liverpool, United Kingdom.
authors: Paul S
authors: PS
authors: McNamara
mesh_terms: D000293:Adolescent; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D065886:Neurodevelopmental Disorders / Q000150:complications / Q000382:microbiology* / Q000503:physiopathology / Q000523:psychology; D009504:Neutrophils / Q000473:pathology; D011788:Quality of Life / Q000523:psychology; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012137:Respiratory System / Q000382:microbiology* / Q000503:physiopathology; D012141:Respiratory Tract Infections / Q000150:complications / Q000382:microbiology* / Q000503:physiopathology / Q000523:psychology; D012720:Severity of Illness Index; D013290:Streptococcal Infections / Q000150:complications / Q000382:microbiology* / Q000503:physiopathology / Q000523:psychology; D034361:Streptococcus mitis / Q000235:genetics / Q000302:isolation & purification; D011795:Surveys and Questionnaires
chemical_list: D012336:RNA, Ribosomal, 16S