Rationale: PZP (pregnancy zone protein) is a broad-spectrum immunosuppressive protein believed to suppress T-cell function during pregnancy to prevent fetal rejection. It has not previously been reported in the airway.Objectives: To characterize PZP in the bronchiectasis airway, including its relationship with disease severity.Methods: Label-free liquid chromatography/mass spectrometry was performed for sputum protein profiling of patients with bronchiectasis confirmed by high-resolution computed tomography. Results for patients with and without Pseudomonas aeruginosa infection were compared. Sputum and serum PZP was measured by validated ELISA. Airway infection status was established by culture and 16S ribosomal RNA sequencing. Immunofluorescence, ELISA, and electron microscopy were used to identify the cellular source of PZP in neutrophils treated with multiple stimuli.Measurements and Main Results: Elevated PZP was identified by label-free liquid chromatography/mass spectrometry as being associated with P. aeruginosa infection. In a validation study of 124 patients, sputum but not serum concentrations of PZP were significantly associated with the Bronchiectasis Severity Index, the frequency of exacerbations, and symptoms. Airway infection with Proteobacteria such as P. aeruginosa was associated with higher concentrations of PZP. PZP in sputum was directly related to airway bacterial load. Neutrophils induced to form neutrophil extracellular traps (NETs) with phorbol myristate acetate released high concentrations of PZP in vitro, and fluorescence microscopy confirmed the presence of PZP in NETs, whereas fluorescence and electron microscopy localized PZP to the cytoplasm and nuclei of neutrophils. Effective antibiotic therapy reduced sputum PZP.Conclusions: PZP is released into NETs. We report a novel link between airway infection, NET formation, and disease severity in bronchiectasis during chronic airway inflammation.

Summary Background Despite decades of use, the actual amounts of topical corticosteroids (TCS) and emollients used in moderate‐to‐severe atopic dermatitis (AD) under real‐world conditions are unknown. Thus, it remains unclear whether inadequate use is widespread. Objectives To quantify the use of TCS and emollients in moderate‐to‐severe AD. Methods Double‐blinded drug prescribing was recorded prospectively at the point of drug dispensing within a catchment area of approximately 450 000 people over a 31‐year period in a population‐based cohort marked by failure of disease control in primary care (n = 844). For each patient, prescribing was recorded over a 12‐month period in order to minimize fluctuations. Results This approach resulted in a near‐complete dataset, which was essentially free of reporting bias and recording bias. Atopic comorbidities matched expected frequencies. Median use of TCS was statistically significantly higher in juvenile patients (age < 16 years) compared with adult patients (49·2 vs. 38·1 g per month), in male vs. female patients (46·8 vs. 29·7 g per month) and in patients receiving concurrent asthma treatment (40·4 vs. 26·7 g per month). TCS use was strongly associated with antidepressant treatment. Emollient use was unexpectedly low with a median of 9·6 g per day (range 1·4–30·1). Results were replicated in an independent validation cohort. Conclusions Deficient use of emollients may be a factor contributing to AD severity. Our analysis showed that the use of TCS does not exceed current guidelines. Accurate quantification of topical treatments provides a widely accessible strategy to measure the real‐world impact of novel AD treatments. What's already known about this topic? Both emollient and topical corticosteroid (TCS) use have been a mainstay of atopic dermatitis (AD) treatment for over 60 years. The actual quantities used by patients under real‐world conditions are unknown. What does this study add? The real‐world use of emollients is fourfold lower than the amount recommended in current guidelines. Underuse of emollients may be a significant factor in disease exacerbation. The use of TCS is significantly higher in male patients and is higher in patients with AD who also have asthma. The use of TCS is strongly associated with concurrent antidepressant treatment.

Background. Despite decades of use, the magnitude of efficacy of narrowband ultraviolet B (NB-UVB) phototherapy for atopic dermatitis (AD) beyond industrysponsored trials remains unclear. Aim. To evaluate the clinical efficacy of NB-UVB in AD under real-world conditions. Methods. We conducted a historical inception cohort study using automated recording of dispensed drugs to provide an objective treatment outcome in a large population catchment of 420 000 people over 15 years. We analysed clinical treatment outcomes, recorded multicentre and prospectively over 15 years, of a large AD treatment cohort (n = 844), along with the drugs dispensed to this cohort. Results. The majority (70%) of patients with AD received significantly fewer topical corticosteroids (TCS) during the 12-month window after finishing NB-UVB compared with the 12-month window before starting the treatment (median reduction from 37.5 to 19.7 g/month). The number of patients dispensed with oral corticosteroids and antihistamines also dropped significantly (from 20% to 10% and from 69% to 31%, respectively), while all AD-unrelated drugs dispensed remained unchanged. Clinically, NB-UVB treatment achieved a 'clear' or 'almost clear' status in 48.7% of patients, while 20.4% achieved 'moderate clearance'. Treatment outcomes scores were validated by a strong correlation with reduction in AD-specific drug treatment. Conclusion. Our data confirm the significant efficacy of NB-UVB for AD under conditions of routine care.

No abstract