key: cord-0915294-ni4qpo89
authors: Ponsford, Mark; Price, Colin; Farewell, Daniel; Greene, Giles; Moore, Catherine; Perry, Michael; Price, Nicky; Cottrell, Simon; Steven, Rachael; El-Shanawany, Tariq; Carne, Emily; Cousins, Richard; Williams, Paul; Schaub, Alexander; Vonarburg, Cedric; Jolles, Stephen
title: Increased respiratory viral detection and symptom burden among patients with primary antibody deficiency: results from the BIPAD study.
date: 2020-08-22
journal: J Allergy Clin Immunol Pract
DOI: 10.1016/j.jaip.2020.08.016
sha: 27b80fceb7ff361c2a22d93cf12c682336b0ced5
doc_id: 915294
cord_uid: ni4qpo89

Abstract Background Patients with primary antibody deficiency (PAD) are at increased risk of respiratory tract infections but our understanding of their nature and consequences remains limited. Objective To define the symptomatic and microbial burden of upper airway infection in adults with PAD relative to age-matched controls. Methods Prospective 12-month observational study consisting of a daily upper and lower airway symptom score alongside fortnightly nasal swab with molecular detection of 19 pathogen targets. Results 44 patients and 42 controls (including 34 household pairs) were recruited, providing over 22,500 days of symptom scores and 1,496 nasal swabs. Swab and questionnaire compliance exceeded 70%. At enrolment, 64% of patients received prophylactic antibiotics with a 34% prevalence of bronchiectasis. On average, PAD patients experienced symptomatic respiratory exacerbations every 6 days compared to 6 weeks for controls, associated with significant impairment of respiratory-specific quality of life scores. Viral detections were associated with worsening of symptom scores from a participant’s baseline. PAD patients had increased odds ratio (OR) for pathogen detection, particularly viral (OR 2.73; 95% CI: 2.09 to 3.57), specifically human rhinovirus HRV (OR 3.60; 2.53-5.13), and parainfluenza (OR 3.06; 1.25-7.50). H. influenzae and S. pneumonia were also more frequent in PAD. Young child exposure, IgM deficiency, and presence of bronchiectasis were independent risk factors for viral detection. Prophylactic antibiotic use was associated with a lower risk of bacterial detection by PCR. Conclusion PAD patients have a significant respiratory symptom burden associated with increased viral infection frequency despite immunoglobulin replacement and prophylactic antibiotic use. This highlights a clear need for future therapeutic trials in the PAD-population, and informs future study design.

Participants were asked to record daily symptoms using a study-specific symptom score (BIPAD-Q) 

Strain-typing of HRV was not performed.

Definitions

Symptomatic respiratory exacerbation (SRE) was defined by a symptom score of 2 or more occurring 159 for ≥2 consecutive days as recorded by the patient, as previously described (11). SRE interval 

Study population 175 A total of 44 PAD patients and 42 healthy controls participated in the study, of which 34 pairs co-176 habited ( Table 1) . PAD incorporated a range of diagnoses ( Table 2) Table 1) . Compliance with routine nasal swab return was 194 72% in PAD patients, and 78% in controls ( Table 1) .

Symptomatic respiratory exacerbations are more frequent in PAD patients representing 50% and 32% of total swabs submitted by these groups respectively. The effect of 216 introducing routine nasal swab sampling for healthy controls was to increase the number of negative 217 swabs (data not shown). Specific pathogen detection rates and odds ratios are summarised in Table   218 3. HRV dominated, with parainfluenza also detectable at greater rate among PAD patients. Viral co-219 detection with bacterial species was found at increased frequency in PAD relative to controls; with 

The most notable finding is the increased rate of detection for common circulating upper respiratory week averages. The Welsh sentinel GP influenza-like illness weekly consultation rate is also 484 provided (e). * Data predominantly (>95%) from hospital patients 485 

The minimal important 367 difference for the St George's Respiratory Questionnaire in patients with severe COPD

Investigating the 370 minimal clinically important difference for SNOT-22 symptom domains in surgically managed chronic 371 rhinosinusitis. International forum of allergy & rhinology

Transmission of the Common Cold to Volunteers 373

Under Controlled Conditions: I. The Common Cold as a Clinical Entity

Dry cotton or flocked respiratory swabs as a simple