African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

/pdf/a-genome-wide-association-search-for-type-2-diabetes-genes-4ewfwh6s3b.pdf

A genome-wide association search for type 2 diabetes genes in African Americans.

Linda Nici, Claudio Donner, Emiel Wouters, Richard Zuwallack, Nicolino Ambrosino, Jean Bourbeau, Mauro Carone, Bartolome Celli, Marielle Engelen, Bonnie Fahy, Chris Garvey, Roger Goldstein, Rik Gosselink, Suzanne Lareau, Neil MacIntyre, Francois Maltais, Mike Morgan, Denis O’Donnell, Christian Prefault, Jane Reardon, Carolyn Rochester, Annemie Schols, Sally Singh, and Thierry Troosters, on behalf of the ATS/ERS Pulmonary Rehabilitation Writing Committee

/pdf/american-thoracic-society-european-respiratory-society-fshcxcru7i.pdf

American Thoracic Society/European Respiratory Society Statement on Pulmonary Rehabilitation

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(09)62116-4.pdf

Chronic obstructive pulmonary disease in non-smokers

Objectives:The Eating Assessment Tool is a self-administered, symptom-specific outcome instrument for dysphagia. The purpose of this study was to assess the validity and reliability of the 10-item ...

Validity and reliability of the Eating Assessment Tool (EAT-10).

### Cough

1) All basic scientific articles should refer to cough as a three-phase motor act. For the purposes of acoustic recordings in clinical studies, however, cough should be described as a forced expulsive manoeuvre or manoeuvres against a closed glottis that are associated with a characteristic sound or sounds.

2) All scientific articles should include a clear definition of what the authors have used as their definition of cough.

### Capsaicin and citric acid inhalation cough challenge

1) The methodology for the performance of inhalation cough challenge should be standardised so as to facilitate universal interpretation and comparison of data generated by different laboratories.

2) Comprehensive normal ranges need to be developed using the standardised methodology advocated in the present document.

3) The single-breath concentration–response method using a flow-limited dosimeter is recommended for most experimental protocols.

4) Both C2 and C5 should be recorded.

5) Since there is wide inter-individual variation, cough challenge data have no intrinsic significance, but may usefully be used to follow change in cough reflex sensitivity in an individual.

### Cough induced by inhalation of aqueous solutions

1) Aerosolised aqueous solutions represent a useful experimental tool in cough research.

2) The cough challenge with ultrasonic distilled water (fog) is difficult to standardise since it is highly dependent upon nebuliser output.

3) Consideration should be given to potential adverse events, such as bronchoconstriction and cross-infection.

### Cough monitors

1) No cough monitor is currently the gold standard.

2) Monitors should be developed that are ambulatory, are capable of being digitally processed and permit prolonged (24-h) recording.

3) There is little to commend any particular method of quantifying cough over any other.

### Assessment of quality of life of patients with chronic cough

1) Cough can have profound effects on health status, which can be assessed by cough-specific health status questionnaires.

2) Cough visual analogue scale (VAS, 0–100 mm) should be used to assess cough severity in patients with chronic cough.

3) Patients with chronic cough should be assessed with cough-specific quality-of-life questionnaires in clinical studies.

### Animal models of cough

1) The most useful animal model of cough is …

/pdf/ers-guidelines-on-the-assessment-of-cough-3gr3n85c88.pdf

ERS guidelines on the assessment of cough

BACKGROUND: Chronic cough is a common condition which has a significant impact on quality of life. Assessment and management are hampered by the absence of well validated outcome measures. The development and validation of the Leicester Cough Questionnaire (LCQ), a self-completed health related quality of life measure of chronic cough, is presented. METHODS: Patients with chronic cough were recruited from outpatient clinics. The development of the LCQ consisted of three phases: phase 1 (item generation); phase 2 (item reduction, allocation of items to domains and validation of questionnaire); phase 3 (repeatability and responsiveness testing of final version of questionnaire). RESULTS: Phase 1: Literature review, multidisciplinary team meeting and 15 structured interviews with chronic cough patients generated 44 items (LCQ1) with a 7 point Likert response scale. Phase 2: 104 chronic cough outpatients completed the LCQ1 along with an importance rating for each item. The clinical impact factor method was used for item reduction to 19 items (LCQ2: final version). These items were divided into three domains (physical, psychological and social) following expert opinion. Internal reliability, as assessed using Cronbach's alpha coefficients, varied between 0.79 and 0.89. Concurrent validity was high when the LCQ2 (n=56) was compared with a cough visual analogue score (r=-0.72). There was a moderate relationship with response to the St George's Respiratory Questionnaire (r=-0.54) and SF36 total score (r=0.46). Phase 3: Two week repeatability (n=24) was high with intraclass correlation coefficients for domains varying between 0.88 and 0.96. Responsiveness in nine patients whose cough was successfully treated varied within domains from an effect size of 0.84 to 1.75. CONCLUSION: The LCQ is a valid, repeatable 19 item self-completed quality of life measure of chronic cough which is responsive to change. It should be a useful tool in clinical trials and longitudinal studies.

https://thorax.bmj.com/content/thoraxjnl/58/4/339.full.pdf

Development of a symptom specific health status measure for patients with chronic cough: Leicester Cough Questionnaire (LCQ)

Cough frequency, cough sensitivity and health status in patients with chronic cough.

Cough and Glottic-Stop Reflex Sensitivity in Health and Disease

Background: Patients with idiopathic chronic cough and unexplained airflow obstruction in non-smokers have been shown to have an increased prevalence of hypothyroidism and other organ specific autoimmune disorders. Whether patients with hypothyroidism have an increased prevalence of respiratory symptoms is unknown.

Methods: The prevalence of respiratory symptoms was assessed in 124 patients with treated hypothyroidism recruited from primary and secondary care, 64 outpatients with inflammatory bowel disease, and 1346 control adults recruited randomly from the electoral register in a case-control study. Respiratory symptoms and smoking history were assessed by a respiratory symptom questionnaire.

Results: After adjustment for age, sex and smoking, symptoms of breathlessness and sputum production were more prevalent in both patient populations than in controls (odds ratios for hypothyroidism and inflammatory bowel disease; breathlessness: 3.1 (95% CI 2.1 to 4.6) and 3.4 (95% CI 2.0 to 6.0), respectively; sputum production: 2.7 (95% CI 1.6 to 4.5) and 2.5 (95% CI 1.2 to 5.0), respectively). Cough during the day and night was significantly more prevalent in patients with hypothyroidism (1.8 (95% CI 1.2 to 2.9)) and approached significance in those with inflammatory bowel disease (1.8 (95% CI 1.0 to 3.4)). Wheeze and nocturnal cough were no more prevalent in either disease population than in controls.

Conclusion: There is a significantly increased prevalence of respiratory symptoms in patients with hypothyroidism or inflammatory bowel disease compared with controls recruited from the general population. Further work is required to determine whether similar differences are seen in comparison with hospital based controls. These findings support the hypothesis that there is a link between autoimmune hypothyroidism and respiratory disease.

https://thorax.bmj.com/content/thoraxjnl/58/6/533.full.pdf

Respiratory symptoms in patients with treated hypothyroidism and inflammatory bowel disease

Tonsillar enlargement is sometimes seen in patients with otherwise unexplained chronic cough although its significance is unclear. In this study, the authors set out to test the hypothesis that cough symptoms and cough reflex sensitivity will improve after tonsillectomy in patients with otherwise unexplained chronic cough and enlarged tonsils. Eight consecutive patients with unexplained chronic cough and enlarged tonsils were recruited from 236 patients seen in a cough clinic between 2000 and 2001. Six patients with enlarged tonsils and no cough who were undergoing tonsillectomy for other reasons were recruited as a control group. All patients rated cough severity on a cough visual analogue score (0-100 mm) and had capsaicin cough reflex sensitivity measurement twice before and again 3 months after tonsillectomy. Patients with a chronic cough had heightened cough reflex sensitivity compared with the control group at baseline. There was a significant improvement in mean cough visual analogue score 3 months after tonsillectomy in patients with chronic cough (mean difference 30 mm; 95% confidence interval of difference 8-51 mm). The geometric mean concentration of capsaicin required to cause five coughs increased from 4 to 207 micromol L(-1) after tonsillectomy in patients with chronic cough (mean difference from baseline 5.6 doubling concentrations; 95% confidence interval of difference 3.1-8.2). There was no change in cough reflex sensitivity in control patients after tonsillectomy. These preliminary findings suggest for the first time a possible role for tonsillectomy in patients with enlarged tonsils in whom other causes of cough have been ruled out.

https://erj.ersjournals.com/content/erj/23/2/199.full.pdf

B Prudon

Papers

Development of a symptom specific health status measure for patients with chronic cough: Leicester Cough Questionnaire (LCQ)

Cough frequency, cough sensitivity and health status in patients with chronic cough.

Cough and Glottic-Stop Reflex Sensitivity in Health and Disease

Respiratory symptoms in patients with treated hypothyroidism and inflammatory bowel disease

Chronic tonsillar enlargement and cough: preliminary evidence of a novel and treatable cause of chronic cough