title: Activity, severity and impact of respiratory disease in primary antibody deficiency syndromes.
abstract: OBJECTIVE
  Some patients with primary antibody deficiency (PAD) syndromes develop bronchiectasis. In immunocompetent patients with bronchiectasis, key clinico-pathophysiological relationships exist between exacerbation frequency, lung function, health-status, infection and inflammation. It is not known whether such relationships are present in PAD. It is also not known how local and systemic inflammation in PAD compares with that in immunocompetent (non-PAD) bronchiectasis patients.
  
  
  METHODS
  We assessed symptoms, exacerbation frequency, health-status, lung function, CT, airway and systemic inflammation and infection in 33 PAD patients and 20 immunocompetent controls with bronchiectasis.
  
  
  RESULTS
  Despite less severe airflow obstruction, PAD patients had similar health-status impairment and greater airway (sputum log10 IL-6 2.71 vs. 1.81 pg/ml, p = 0.001) and greater systemic inflammation than immunocompetent bronchiectasis controls (serum log10 CRP 0.77 vs. 0.36 mg/l, p = 0.001). In PAD, cross-sectional markers of disease severity (CT and lung function) did not relate to inflammatory markers of disease activity, however there was a relationship between FEV1 decline rate and systemic inflammation (IL-6; r = 0.42, p = 0.036) and the magnitude of the systemic inflammatory response was related to that in the airway. Correlation between generic SF36 and respiratory SGRQ questionnaires (r = -0.79, p < 0.001) suggests that much health-status impairment in PAD relates to respiratory involvement. Health-status was associated with dyspnoea (rho = 0.77, p < 0.001), respiratory infection frequency (rho = 0.48, p = 0.016), lung function (FEV1: r = -0.60, p = 0.001) and rate of lung function decline (r = 0.41, p = 0.047).
  
  
  CONCLUSIONS
  The major findings of this analysis are that in patients with PAD, cross-sectional markers of disease severity such as lung function and CT extent of disease do not reflect disease activity as assessed by airway and systemic inflammation. In addition, there is a relationship between the rate of progression of lung disease and the severity of the systemic inflammatory response which itself is related to that in the airway. Much of the quality of life impact in PAD relates to respiratory involvement, specifically the severity of airflow obstruction, respiratory exacerbation frequency and dyspnoea. Finally, patients with PAD had greater airway and systemic inflammation than a control population with non-PAD bronchiectasis which may suggest a dysregulated airway immune response.
authors.affiliation: UCL Respiratory Medicine, University College London, London, UK, j.hurst@ucl.ac.uk.
authors.forename: John R
authors.initials: JR
authors.lastname: Hurst
authors.forename: Sarita
authors.initials: S
authors.lastname: Workman
authors.forename: Davinder S
authors.initials: DS
authors.lastname: Garcha
authors.forename: Suranjith L
authors.initials: SL
authors.lastname: Seneviratne
authors.forename: Jamanda A
authors.initials: JA
authors.lastname: Haddock
authors.forename: Bodo
authors.initials: B
authors.lastname: Grimbacher
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D001987:Bronchiectasis / Q000150:complications / Q000175:diagnosis; D005260:Female; D006801:Humans; D007136:Immunoglobulins; D007153:Immunologic Deficiency Syndromes / Q000150:complications*; D008168:Lung / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012129:Respiratory Function Tests; D012140:Respiratory Tract Diseases / Q000150:complications* / Q000175:diagnosis* / Q000382:microbiology; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed
chemical_list: D015415:Biomarkers; D007136:Immunoglobulins