Primary Ciliary Dyskinesia:Integrating Genetics into Clinical Practice

Purpose of Review: Advances in molecular genetics have improved our understanding of primary ciliary dyskinesia. The purpose of this review is to describe the integration of genetics into clinical practice.Recent Findings: This review describes > 50 genes which have been identified to cause multiple motile ciliopathies. Known genotype–phenotype relationships are explored, including genes associated with worse prognosis (CCDC39, CCDC40, CCNO). Features which indicate referral for genetic testing such as a family history, situs defects and lifelong chronic upper and lower respiratory tract disease are described along with how genetics fits into current guidelines for diagnostic algorithms, and the potential challenges and advantages.Summary: As we move forward, the growing genomic knowledge about primary ciliary dyskinesia will aid diagnosis, understanding of prognosis and the establishment of future therapeutic trials

Primary Ciliary Dyskinesia:Integrating Genetics into Clinical Practice

Purpose of Review: Advances in molecular genetics have improved our understanding of primary ciliary dyskinesia. The purpose of this review is to describe the integration of genetics into clinical practice.Recent Findings: This review describes > 50 genes which have been identified to cause multiple motile ciliopathies. Known genotype–phenotype relationships are explored, including genes associated with worse prognosis (CCDC39, CCDC40, CCNO). Features which indicate referral for genetic testing such as a family history, situs defects and lifelong chronic upper and lower respiratory tract disease are described along with how genetics fits into current guidelines for diagnostic algorithms, and the potential challenges and advantages.Summary: As we move forward, the growing genomic knowledge about primary ciliary dyskinesia will aid diagnosis, understanding of prognosis and the establishment of future therapeutic trials

A point of care neutrophil elastase activity assay identifies bronchiectasis severity, airway infection and risk of exacerbation

Introduction: Neutrophil elastase activity in sputum can identify patients at high risk of airway infection and exacerbations in bronchiectasis. Application of this biomarker in clinical practice is limited, because no point-of-care test is available. We tested whether a novel semi-quantitative lateral flow device (neutrophil elastase airway test stick - NEATstik\uae) can stratify bronchiectasis patients according to severity, airway infection and exacerbation risk. Methods: Sputum samples from 124 patients with stable bronchiectasis enrolled in the UK and Spain were tested using the NEATstik\uae, which scores neutrophil elastase concentration from 0 (<8 \u3bcg\ub7mL-1 elastase activity) to 10 (maximum detectable neutrophil elastase activity). High neutrophil elastase activity was regarded as a NEATstik\uae grade >6. Severity of disease, airway infection from sputum culture and exacerbations over the 12 months were recorded. An independent validation was conducted in 50 patients from Milan, Italy. Measurements and main results: Patients had a median age of 69 years and forced expiratory volume in 1 s (FEV1) 69%. High neutrophil elastase activity was associated with worse bronchiectasis severity using the bronchiectasis severity index (p=0.0007) and FEV1 ( p=0.02). A high NEATstik\uae grade was associated with a significant increase in exacerbation frequency, incident rate ratio 2.75 (95% CI 1.63-4.64, p<0.001). The median time to next exacerbation for patients with a NEATstik\uae grade >6 was 103 days compared to 278 days. The hazard ratio was 2.59 (95% CI 1.71-3.94, p<0.001). Results were confirmed in the independent validation cohort. Conclusions: A novel lateral flow device provides assessment of neutrophil elastase activity from sputum in minutes and identifies patients at increasing risk of airway infection and future exacerbations

Compassion satisfaction and compassion fatigue in Australian emergency nurses:A descriptive cross-sectional study

Introduction: Emergency nurses are at risk of compassion fatigue. Compassion fatigue caused by exposure to suffering may compromise the individual's personal wellbeing and reduce work efficiency. Methods: A quantitative cross-sectional survey with open responses was conducted using the Professional Quality of Life: Compassion Satisfaction and Compassion Fatigue (ProQOL) scale and open-ended questions. Responses from a convenience sample of 86 nurses from two hospital emergency departments in Victoria, Australia, were analysed. Results: The median score for Compassion Satisfaction was 78% with all nurses reporting average to high scores. Most had average levels of Compassion Fatigue: Burnout median score was 53% and Secondary Traumatic Stress median score 49%. No statistically significant correlation was found between scales nor with influencing demographic characteristics. A qualification in emergency nursing was predictive of Compassion Satisfaction. Six descriptive job-associated factors contributed to nurses' stress: human resources, the organisation, job-specific components, patient mix and professional and personal components. Conclusion/s: Average to high levels of Compassion Satisfaction and low to average levels of Compassion Fatigue were found in emergency nurses. Issues contributing to stress were work and role related. An understanding of these stressors may help nurses and nurse managers to ameliorate emergency nurses' levels of stress and help limit staff burnout

Restoring ciliary function:Gene therapeutics for primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a genetic disease characterized by defects in motile cilia, which play an important role in several organ systems. Lung disease is a hallmark of PCD, given the essential role of cilia in airway surface defense. Diagnosis of PCD is complicated due to its reliance on complex tests that are not utilized by every clinic and also its phenotypic overlap with several other respiratory diseases. Nonetheless, PCD is increasingly being recognized as more common than once thought. The disease is genetically complex, with several genes reported to be associated with PCD. There is no cure for PCD, but gene therapy remains a promising therapeutic strategy. In this review, we provide an overview of the clinical symptoms, diagnosis, genetics, and current treatment regimens for PCD. We also describe PCD model systems and discuss the therapeutic potential of different gene therapeutics for targeting the intended cellular target, the ciliated cells of the airway.</p

Who goes there? Social surveillance as a response to intergroup conflict in a primitive termite

Thompson FJ, Hunt KL, Wright K, et al. Who goes there? Social surveillance as a response to intergroup conflict in a primitive termite. Biology Letters. 2020;16(7): 20200131.Intergroup conflict has been suggested as a major force shaping the evolution of social behaviour in animal groups. A long-standing hypothesis is that groups at risk of attack by rivals should become more socially cohesive, to increase resilience or protect against future attack. However, it is usually unclear how cohesive behaviours (such as grooming or social contacts) function in intergroup conflict. We performed an experiment in which we exposed young colonies of the dampwood termite,Zootermopsis angusticollis, to a rival colony while preventing physical combat with a permeable barrier. We measured social contacts, allogrooming and trophallaxis before, during and after exposure. Termites showed elevated rates of social contacts during exposure to a rival compared to the pre-exposure phase, but rates returned to pre-exposure levels after colonies were separated for 9 days. There was evidence of a delayed effect of conflict on worker trophallaxis. We suggest that social contacts during intergroup conflict function as a form of social surveillance, to check individual identity and assess colony resource holding potential. Intergroup conflict may increase social cohesion in both the short and the long term, improving the effectiveness of groups in competition

Inflammatory and mucociliary dysfunction based endotypes across the spectrum of chronic airways diseases

Introduction: There is substantial overlap between COPD, asthma, bronchiectasis(BE) and cystic fibrosis(CF) and each is characterised by inflammation and mucociliary dysfunction.Hypothesis: Biology, rather than disease labels, may stratify patients into therapeutically relevant subtypes.Methods: Patients were categorized by primary disease and clinical characteristics, spontaneous sputum was collected and inflammatory characteristics (neutrophil elastase(NE) and 19 cytokines) and sputum properties (DNA content, mucins, rheology, dry weight) measured. K-means clustering was performed and parameters compared between and within disease groups. Smokers without respiratory disease were used as controls.Results: The study included patients with asthma(76), COPD(91), BE(54), CF(24) and controls(26). 10 cytokines, NE, dry weight, mucins and multiple sputum parameters were different between disease groups and healthy controls (p&lt;0.05). K means clustering identified 2 clusters defined by neutrophilic (N) or eosinophilic (E) inflammation. The E cluster was associated with lower dry weight, DNA content and higher mucins, particularly MUC5B. The rheology parameters G’ and G* were significantly higher in the E group while Tan(delta) was higher in the N group (p&lt;0.05 all comparisons). Both clusters were present in all disease groups with more neutrophilic inflammation in CF and BE (42% of COPD patients and 46% of asthma patients were neutrophilic vs 78% of BE and 87% of CF,p&lt;0.0001).Conclusion: Airways diseases have heterogenous inflammatory and mucus parameters. Assessment based on disease labels may be aided by endotyping using inflammatory and mucociliary clearance parameters

Inflammatory and mucociliary dysfunction based endotypes across the spectrum of chronic airways diseases

Introduction: There is substantial overlap between COPD, asthma, bronchiectasis(BE) and cystic fibrosis(CF) and each is characterised by inflammation and mucociliary dysfunction.Hypothesis: Biology, rather than disease labels, may stratify patients into therapeutically relevant subtypes.Methods: Patients were categorized by primary disease and clinical characteristics, spontaneous sputum was collected and inflammatory characteristics (neutrophil elastase(NE) and 19 cytokines) and sputum properties (DNA content, mucins, rheology, dry weight) measured. K-means clustering was performed and parameters compared between and within disease groups. Smokers without respiratory disease were used as controls.Results: The study included patients with asthma(76), COPD(91), BE(54), CF(24) and controls(26). 10 cytokines, NE, dry weight, mucins and multiple sputum parameters were different between disease groups and healthy controls (p&lt;0.05). K means clustering identified 2 clusters defined by neutrophilic (N) or eosinophilic (E) inflammation. The E cluster was associated with lower dry weight, DNA content and higher mucins, particularly MUC5B. The rheology parameters G’ and G* were significantly higher in the E group while Tan(delta) was higher in the N group (p&lt;0.05 all comparisons). Both clusters were present in all disease groups with more neutrophilic inflammation in CF and BE (42% of COPD patients and 46% of asthma patients were neutrophilic vs 78% of BE and 87% of CF,p&lt;0.0001).Conclusion: Airways diseases have heterogenous inflammatory and mucus parameters. Assessment based on disease labels may be aided by endotyping using inflammatory and mucociliary clearance parameters