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point and counterpoint 
Ariane Lewis, MD; David Greer, MD, MA
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No abstract is available for this article
point and counterpoint 
Robert D. Truog, MD; Robert C. Tasker, MA, MD, FRCP
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No abstract is available for this article
point and counterpoint 
Robert D. Truog, MD; Robert C. Tasker, MA, MD, FRCP
Topics: , , , , , , , , ,
No abstract is available for this article
point and counterpoint 
Ariane Lewis, MD; David Greer, MD, MA
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No abstract is available for this article
original research 
Hui-Bin Huang, MD; Jin-Min Peng, MD; Biao Xu, MD; Guang-Yun Liu, MD; Bin Du, MD
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Background  Endotracheal intubation (EI) in intensive care unit (ICU) patients is associated with an increased risk of life-threatening adverse events due to unstable conditions, rapid deterioration, limited preparation time, and variability in expertise of operators. We aimed to compare the effect of video laryngoscopy (VL) and direct laryngoscopy (DL) in ICU patients requiring EI.

Methods  We searched for relevant studies in PubMed, Embase, and the Cochrane database from inception up to Jan 30, 2017. Randomized controlled trials (RCTs) were included if they reported data on any of the predefined outcomes in ICU patients requiring EI and managed with VL or DL. Results were expressed as risk ratio (RR) or mean difference (MD) with accompanying 95% confidence interval (CI).

Results  Five RCTs with 1,301 patients were included. Despite better glottic visualization with VL (RR = 1.24; 95% CI, 1.07 to 1.43; P = 0.003), use of VL did not result in a significant increase in first-attempt success rate (RR = 1.08; 95% CI, 0.92 to 1.26; P = 0.35) when compared with DL. In addition, time to intubation (MD = 4.12 seconds; 95% CI, -15.86 to 24.09; P = 0.69), difficult intubation (RR = 0.72, 95% CI, 0.30 to 1.70; P = 0.45), mortality (RR = 1.02, 95% CI, 0.84 to 1.25; P = 0.83), and most other complications were similar between VL and DL groups.

Conclusions  VL technique did not increase first-attempt success rate during EI in ICU patients compared with DL. These findings do not support routine use of VL in ICU patients.

original research 
Brian S. Furukawa, MD; Nicholas J. Pastis, MD; Nichole T. Tanner, MD; Alexander Chen, MD; Gerard A. Silvestri, MD
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Background  Electromagnetic navigational bronchoscopy (ENB) is guided-bronchoscopy to pulmonary nodules (PN) which relies on a pre-procedural chest CT to create a 3-dimensional (3-D) virtual airway map. The CT is traditionally done at a full inspiratory breath hold (INSP) but the procedure is performed while the patient tidal breaths, where lung volumes are closer to functional residual capacity. Movement of a PN from INSP to expiration (EXP) has been shown to average 17.6 mm. Therefore, the hypothesis of this study is that pre-procedural virtual maps built off a CT closer to physiological lung volumes during bronchoscopy may better represent the actual 3-D location of a PN.

Methods  Consecutive patients with a PN needing a histological diagnosis were enrolled. A pre-procedure INSP and EXP CT scan were obtained to create two virtual maps. During the airway inspection, the system tracked the sensor probe to collect 3-D points which were reconstructed into the lumen registration map. This map is thought to best represent the patient’s airways during bronchoscopy. Predicted PN location on an EXP and INSP map was compared with lumen registration.

Results  Twenty consecutive PN underwent ENB. The predicted PN location, as compared with lumen registration, was significantly closer on EXP vs. INSP (4.5 mm ± 3.3 mm vs. 14.8 mm ± 9.7 mm; p < 0.0001).

Conclusions  Predicted 3-D nodule location using an EXP scan for ENB is significantly closer to actual nodule location when compared with an INSP scan, but whether this leads to increase yields needs to be determined.

original research 
Julie Morisset, MD; Eric Vittinghoff, PhD; Brett M. Elicker, MD; Xiaowen Hu, MD; Stephanie Le, MD; Jay H. Ryu, MD; Kirk D. Jones, MD; Anna Haemel, MD; Jeffrey A. Golden, MD; Francesco Boin, MD; Brett Ley, MD; Paul J. Wolters, MD; Talmadge E. King, Jr., MD; Harold R. Collard, MD FCCP; Joyce S. Lee, MD
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Rationale  Interstitial lung disease (ILD) is an important cause of morbidity and mortality in scleroderma (Scl). Risk prediction and prognostication in Scl-ILD patients is challenging because of heterogeneity in the disease course.

Methods  We aimed to develop a clinical mortality risk prediction model for Scl-ILD. Patients with Scl-ILD were identified from two ongoing longitudinal cohorts: 135 patients at the University of California, San Francisco (UCSF, derivation cohort) and 90 patients at the Mayo Clinic (validation cohort). Using these two separate cohorts, a mortality risk prediction model was developed and validated by testing every potential candidate Cox model, each including 3 or 4 variables of a possible 19 clinical predictors, for time to death. Model discrimination was assessed using the c-index.

Results  Three variables were included in the final risk prediction model (SADL): ever Smoking history, Age, and DLco %-predicted. This continuous model had similar performance in the derivation (c-index=0.88) and validation (c-index=0.84) cohorts. We created a point scoring system using the combined cohort (c-index=0.82), and used it to identify a classification with low, moderate and high mortality risk at 3 years.

Conclusion  The SADL model uses simple, readily accessible clinical variables to predict all-cause mortality in Scl-ILD.

original research 
Dongquan Liu, PhD; Jeff Armitstead, PhD; Adam Benjafield, PhD; Shiyun Shao, PhD; Atul Malhotra, MD; Peter A. Cistulli, MD PhD; Jean-Louis Pepin, MD PhD; Holger Woehrle, MD
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Background  Emergence of central sleep apnea (CSA) during positive airway pressure (PAP) therapy has been observed clinically in ≈10% of OSA titration studies. This study assessed a PAP database to investigate trajectories of treatment-emergent CSA during continuous PAP (CPAP) therapy.

Methods  US telemonitoring device data were analyzed for the presence/absence of emergent CSA at baseline (Week 1) and Week 13. Defined groups were: obstructive sleep apnea (OSA; average central apnea index [CAI] <5/hour in Week 1, <5/hour in Week 13); transient CSA (CAI ≥5/hour in Week 1, <5/hour in Week 13); persistent CSA (CAI ≥5/hour in Week 1, ≥5/hour in Week 13); emergent CSA (CAI <5/hour in Week 1, ≥5/hour in Week 13).

Results  133,006 patients used CPAP for ≥90 days and had ≥1 day with use of ≥1 hour in Week 1 and Week 13. The proportion of patients with CSA in Week 1 or Week 13 was 3.5%; Of these, CSA was transient, persistent or emergent in 55.1%, 25.2% and 19.7%, respectively. Patients with versus without treatment-emergent CSA were older, had higher residual AHI and CAI at Week 13, and more leaks (all p<0.001). Patients with any treatment-emergent CSA were at higher risk of therapy termination versus those who did not develop CSA (all p<0.001).

Conclusions  Our study identified a variety of CSA trajectories during CPAP therapy, identifying several different clinical phenotypes. Identification of treatment-emergent CSA by telemonitoring could facilitate early intervention to reduce the risk of therapy discontinuation and shift to more efficient ventilator modalities.

original research 
Yunus Çolak, MD, PhD; Børge G. Nordestgaard, MD, DMSc; Lars C. Laursen, MD, DMSc; Shoaib Afzal, MD, PhD; Peter Lange, MD, DMSc; Morten Dahl, MD, DMSc, PhD

Background  Risk factors for chronic cough in the general population have not been described systematically. We identified and ranked chronic cough risk factors at the individual and community level using data from 14669 individuals from the Copenhagen General Population Study.

Methods  Severity of chronic cough was assessed using the Leicester Cough Questionnaire(LCQ). We ranked chronic cough risk factors based on magnitude of age-adjusted odds ratios(ORs) at the individual level and of the population attributable risks(PARs) at the community level.

Results  Prevalence of chronic cough in the general population was 4% overall and 3% in never-smokers, 4% in former smokers, and 8% in current smokers. Median score of the LCQ was 5.8(25 and 75 percentiles:5.0-6.3) for physical domain, 5.6(4.6-6.3) for psychological domain, 6.3 (5.5-6.8) for social domain, and 17.3(15.4-18.9) in total. At the level of the individual, age-adjusted ORs for the three top ranked risk factors were 5.0(95% CI:1.4-18) for bronchiectasis, 2.6(1.7-3.9) for asthma and 2.3(1.5-3.4) for gastroesophageal reflux disease in never-smokers, 7.1(2.6-20) for bronchiectasis, 3.1(2.2-4.4) for asthma and 2.2(1.5-3.2) for occupational exposure to dust/fumes in former smokers, and 1.9(1.3-2.9) for airflow limitation in current smokers. At the level of the community, the three top ranked risk factors were female sex (PAR:19%), asthma (10%) and gastroesophageal reflux disease (8%) in never-smokers, abdominal obesity (20%), low income (20%) and asthma (13%) in former smokers, and airflow limitation (23%) in current smokers.

Conclusions  Risk factors for chronic cough differ at the level of the individual and community, and by smoking status. Strategies to prevent and treat modifiable chronic cough risk factors should be tailored accordingly.

original research 
Elliott D. Crouser, M.D.; Joseph E. Parrillo, M.D.; Christopher Seymour, M.D.; Derek C. Angus, M.D, M.P.H.; Keri Bicking, Pharm. D.; Liliana Tejidor, Ph.D.; Robert Magari, Ph.D.; Diana Careaga; JoAnna Williams, M.D.; Douglas R. Closser, M.D.; Michael Samoszuk, M.D.; Luke Herren; Emily Robart; Fernando Chaves, M.D.
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Background  Sepsis most often presents to the emergency department (ED), and delayed detection is harmful. The white blood count (WBC) is often used to detect sepsis, but changes in WBC size also correspond with sepsis. We sought to determine if volume increases of circulating immune cells adds value to the WBC for early sepsis detection in the ED.

Methods  A blinded, prospective cohort study was conducted in two different ED populations within a large academic hospital.

Results  Neutrophil and monocyte volume parameters were measured in conjunction with routine CBC testing on a UniCel® DxH 800 analyzer at the time of ED admission and were evaluated for the detection of sepsis. 1320 ED subjects were consecutively enrolled and categorized as controls (n=879), systemic inflammatory response syndrome (SIRS) (n=203), infection (n=140), or sepsis (n=98). Compared to other parameters, monocyte distribution width (MDW) best discriminated sepsis from all other conditions [AUC 0.79 (95% CI: 0.73-0.84)]; sensitivity 0.77, specificity 0.73; MDW threshold of 20.50.], sepsis from SIRS [AUC 0.74 (95% CI: 0.67-0.84)] and severe sepsis from non-infected ED patients [AUC 0.88 (95% CI: 0.75-0.99); NPV 99%]. The added value of MDW to WBC was statistically significant (AUC 0.89 for MDW + WBC vs 0.81 for WBC alone; p < 0.01); and a decision curve analysis also showed improved performance compared to WBC alone.

Conclusions  The incorporation of MDW with WBC is shown in this prospective cohort study to improve detection of sepsis compared to WBC alone at the time of admission in the ED.

commentary 
John Y. Rhee, MPH; Katharine A. Callaghan, MD; Philip Allen, BS; Amanda Stahl, BS; Martin T. Brown, BS; Alexandra Tsoi, BS; Grace McInerney, BS; Ana-Maria G. Dumitru, PhD
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Physician assisted suicide and euthanasia (PAS/E) has been increasingly discussed and debated in the public square, including in professional medical organizations. However, the medical student perspective on the debate has been essentially absent. We present a medical student perspective on the PAS/E debate as future doctors and those about to enter the profession. We argue that PAS/E is not in line with the core principles of medicine, and the focus should rather be on providing high-quality end-of-life and palliative care.

contemporary reviews in sleep medicine 
Mona M. Hamoda, BDS, MSc, MHSc; Yuuya Kohzuka, DDS; Fernanda R. Almeida, DDS, MSc, PhD
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Oral appliances (OAs) are becoming increasingly recognized not only as an alternative, but also possibly as an adjunct treatment modality for obstructive sleep apnea (OSA). Compared to Continuous Positive Airway Pressure (CPAP), the gold standard therapy, OAs are less efficacious but are more accepted and tolerated by the patients which may in turn lead to a comparable therapeutic effectiveness. Different oral appliance designs currently exist and even more are constantly emerging. Additionally, state of the art technologies are being utilized in the fabrication of many however, all the currently available OAs employ the same mechanism of action by targeting the anatomical component involved in the pathogenesis of the disease. Furthermore, the scope of use of OAs is expanding to encompass more than just the dentate patients but to also include edentulous patients.

For OA patients, the dentist is a member of an interdisciplinary team managing OSA and constant communication and follow up with the sleep physician and other team members is necessary for disease management.

contemporary reviews in sleep medicine 
Jayne C. Carberry, Ph.D; Jason Amatoury, Ph.D; Danny J. Eckert, Ph.D

Obstructive sleep apnea (OSA) is a heterogeneous disorder. If left untreated, OSA has major health, safety and economic consequences. In addition to varying levels of impairment in pharyngeal anatomy (narrow/collapsible airway), non-anatomical ‘phenotypic traits’ are also important contributors to OSA for most patients. However, the majority of existing therapies only target the anatomical cause (e.g. continuous positive airway pressure [CPAP], oral appliances, weight loss, positional therapy, and upper airway surgery). These are typically administered as monotherapy according to a trial and error management approach in which the majority of patients are first prescribed CPAP. Despite its high effectiveness, CPAP adherence remains unacceptably low and second-line therapies have variable and unpredictable efficacies. Recent advances in knowledge of the multiple causes of OSA using respiratory phenotyping techniques have identified new targets or ‘treatable traits’ to direct therapy. Identification of the traits and development of therapies that selectively target one or more of the treatable traits has the potential to personalize the management of this chronic health condition to optimize patient outcomes according to precision medicine principles. This brief review highlights the latest developments and emerging therapies for personalized management approaches for OSA.

recent advances in chest medicine 
Sergio Harari, MD; Davide Elia, MD; Marc Humbert, MD, PhD
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Pulmonary hypertension (PH) due to chronic lung diseases is associated with a poor prognosis, regardless of the underlying respiratory condition. Updated PH guidelines recommend optimal treatment of the underlying lung disease, including long-term oxygen therapy, in patients with chronic hypoxaemia despite the lack of randomized controlled clinical trials supporting this statement. So far, randomized controlled trials on drugs approved for pulmonary arterial hypertension (PAH) have yielded discouraging results in both interstitial lung diseases (ILD) and chronic obstructive pulmonary diseases (COPD) with PH. In some cases, the trials were terminated because of an increase in death and other major adverse events in the active treatment arm versus placebo. In cases of PH due to idiopathic pulmonary fibrosis (IPF), new investigative therapies use a combination of novel antifibrotic treatments and other treatments approved for PAH. The choice of robust end points as well as a target group of patients with specific haemodynamic criteria may help in the selection of innovative therapeutic strategies. The aim of this review is to discuss recent studies and clinical trials for the treatment of PH due to the main chronic respiratory diseases and discuss possible future scenarios for the evaluation of new therapeutic strategies.

translating basic research into clinical practice 
Emma H. Baker, PhD, FRCP; Deborah L. Baines, PhD
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In health, the glucose concentration of airway surface liquid (ASL) is 0.4mM, around 12 times lower than blood glucose concentration. Airway glucose homeostasis is a set of processes that actively maintain low ASL glucose concentration against the transepithelial gradient. Tight junctions between airway epithelial cells restrict paracellular glucose movement. Epithelial cellular glucose transport and metabolism removes glucose from ASL. Low ASL glucose concentrations make an important contribution to airways defence against infection, limiting bacterial growth by restricting nutrient availability.

Both airway inflammation, which increases glucose permeability of tight junctions, and hyperglycaemia, which increases the transepithelial glucose gradient, increase ASL glucose concentrations, with the greatest effect seen where they co-exist. Elevated ASL glucose drives proliferation of bacteria able to use glucose as a carbon source, including Staphylococcus aureus, Pseudomonas aeruginosa and gram-negative bacteria. Clinically this appears to be important in driving exacerbations of chronic lung disease, especially in patients with comorbid diabetes mellitus. Drugs can restore airway glucose homeostasis by reducing permeability of tight junctions (e.g. metformin), increasing epithelial cell glucose transport (e.g. beta agonists, insulin) and/or by lowering blood glucose (e.g. dapagliflozin). In cell culture and animal models these reduce ASL glucose concentrations and limit bacterial growth, preventing infection. Observational studies in humans indicate that airway glucose homeostasis modifying drugs could prevent chronic lung disease exacerbations if tested in randomised trials.

original research  OPEN ACCESS
Pallavi Bedi, MD; James D. Chalmers, PhD; Catriona Graham, MSc; Andrea Clarke, MSc; Samantha Donaldson, BSc; Catherine Doherty, PhD; John RW. Govan, DSc; Donald J. Davidson, PhD; Adriano G. Rossi, DSc; Adam T. Hill, MD
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Introduction  There are no randomised control trials of statin therapy in patients with severe bronchiectasis, chronically infected with Pseudomonas aeruginosa.

Methods  32 patients chronically infected with P. aeruginosa were recruited in this double blind cross over RCT. 16 patients were recruited in each arm, given atorvastatin 80mg or placebo for 3months, followed by a washout period for 6weeks, crossed over and administered the alternative therapy for 3months.

Results  27 patients completed the study. Atorvastatin did not significantly improve the primary endpoint of cough as measured by Leicester Cough Questionnaire [mean difference=1.92, 95% CI for difference (-0.57, 4.41), p=0.12]. However, atorvastatin treatment resulted in improved St Georges Respiratory Questionnaire (-5.62points, p=0.016), reduced serum CXCL8 (p=0.04), TNF (p=0.01) and ICAM1 (p=0.04). There was a trend towards improvement in serum CRP and serum neutrophil counts (p=0.07 and p=0.06 respectively).In vitro, we demonstrated that atorvastatin 10μM reduced fMLF induced upregulation of CD11b expression and changes in calcium flux reflecting an ability to decrease neutrophil activation.

Conclusion  We demonstrated that atorvastatin reduced systemic inflammation and improved quality of life in bronchiectasis patients infected with P. aeruginosa. These effects may be due to an ability of atorvastatin to modulate neutrophil activation.

original research 
Aaron B. Waxman, MD, PhD; Hugh T. McElderry, MD; Mardi Gomberg-Maitland, MD, MSc; Martin C. Burke, DO; Edgar L. Ross, MD; Malcolm M. Bersohn, MD, PhD; Sanjog S. Pangarkar, MD; James H. Tarver, MD; Diane L. Zwicke, MD; Jeremy P. Feldman, MD; Murali M. Chakinala, MD; Robert P. Frantz, MD; Geoffrey B. Thompson, MD; Fernando Torres, MD; Richard L. Rauck, MD; Kathy Clagg, RN; Louise Durst, RN; Pei Li; Marty Morris; Kara L. Southall; Leigh Peterson; Robert C. Bourge, MD
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Background  Prostacyclins improve symptoms and survival in pulmonary arterial hypertension (PAH). In response to risks associated with external delivery systems, an implantable intravenous infusion system was developed. A multicenter, prospective, single-arm, clinical trial (DelIVery for PAH) was conducted to evaluate this system for treprostinil in PAH. This analysis describes the findings related to the implant procedure.

Methods  Patients (n=64) with PAH (WHO Group 1) receiving stable intravenous treprostinil were enrolled. Patients were transitioned to a temporary peripheral intravenous infusion catheter prior to the procedure. System implantation was performed at 10 centers under general anesthesia or deep intravenous sedation by clinicians from various specialties. Central venous access was via the cephalic, subclavian, jugular or axillary vein. Using an introducer and fluoroscopic guidance, the distal tip of the infusion catheter was placed at the superior caval-atrial junction. The catheter was tunneled from the venous access site to an abdominal subcutaneous pocket where the pump was placed.

Results  Of the 64 patients enrolled, four exited prior to implant. All 60 implant procedures were successful. At baseline, all patients were receiving treprostinil via an external pump at a mean dose of 71.4 ± 27.8 ng/kg/min (range 22 to 142 ng/kg/min). The implant averaged 102 ± 32 minutes (range 47 to 184 minutes). Clinically significant implant procedure-related complications included 1 pneumothorax, 2 infections and 1 episode of atrial fibrillation. There were 3 post-implant catheter dislocations in 2 patients. Common implant-related events that were not complications included implant site pain (83%) and bruising (17%).

Conclusion  The procedure for inserting a fully implantable system for treprostinil was successfully performed with few complications.

original research 
Connie G. Glasgow, BA; Gustavo Pacheco-Rodriguez, PhD; Wendy K. Steagall, PhD; Mary E. Haughey, RN, BSN; Patricia A. Julien-Williams, BSN, MSN-CRNP; Mario P. Stylianou, PhD; Bernadette R. Gochuico, MD; Joel Moss, MD, PhD
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Background  Lymphangioleiomyomatosis (LAM) is a destructive lung disease of women caused by proliferation of neoplastic-like LAM cells, with mutations in the TSC1/2 tumor suppressor genes. Based on case reports, CA-125 (an ovarian cancer biomarker) can be elevated in LAM patients. We hypothesized that elevated serum CA-125 levels seen in some LAM patients were due to LAM, not other malignancies, and might respond to sirolimus treatment.

Methods  Serum CA-125 levels were measured for 241 patients at each visit. Medical records were reviewed for co-morbidities, disease progression, and response to sirolimus treatment. CA-125 expression in LAM cells was determined by immunohistochemistry.

Results  Almost 25 percent of LAM patients had at least one elevated serum CA-125 measurement. Higher serum CA-125 levels correlated with lower FEV1, premenopausal status, and pleural effusion in a multivariate model (each p<0.001). Serum CA-125 levels decreased after sirolimus treatment (p=0.002). CA-125 and alpha smooth muscle actin were co-expressed in LAM lung nodules.

Conclusions  Higher serum CA-125 levels are associated with pleural effusions and reduced pulmonary function and are decreased by sirolimus therapy. LAM cells express CA-125. Some elevated serum CA-125 levels may reflect serosal membrane involvement.

translating basic research into clinical practice 
Elisabeth H. Bel, MD, PhD; Anneke ten Brinke, MD, PhD
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Asthma and chronic obstructive airways disease (COPD) are prevalent chronic inflammatory airway diseases that are responsible for a large global disease burden. Both diseases are complex and heterogeneous, and are increasingly recognized as overlapping syndromes that may share similar pathophysiologic mechanisms and treatable traits. Eosinophilic airway inflammation is considered the most influential treatable trait of chronic airway disease, and over the last decade several monoclonal antibodies and small molecule therapies have been developed to target this trait. These include monoclonal antibodies against IL-5 or IL-5 receptor alpha (mepolizumab, reslizumab, benralizumab), IL-13 (lebrikizumab, tralokinumab), IL-4 receptor alpha (dupilumab), Immune globuline E (IgE) (omalizumab), anti-Thymic Stromal Lymphopoitin (TSLP) (tezepelumab) and small molecule therapies such as prostaglandin D2 blockers (fevipiprant, timapiprant). Although these novel biologics have shown promising results in many asthmatics and COPD patients with eosinophilic airway inflammation, it is evident that not all patients respond equally well, despite similar clinical, functional and inflammatory characteristics. This heterogeneity in treatment response is probably related to different molecular pathways or endotypes leading to eosinophilic airway inflammation including adaptive immune pathways mediated by T helper2 (Th2) cells, and innate immune pathways mediated by innate lymphoid cells (ILC2). The relative contribution of these pathways in asthma and COPD is not yet clarified, and there are currently no reliable biomarkers that represent the different pathways. Therefore there is an urgent need for easily measurable and reproducible biomarkers that are linked to underlying pathophysiological disease mechanisms and can predict and monitor responses to novel biologic agents.

translating basic research into clinical practice 
Jennifer A. Keller, BSc(Hons); Alice E. McGovern, PhD; Stuart B. Mazzone, PhD
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Chronic cough is a significant problem and in many patients’ cough remains refractive to both disease specific therapies and current cough suppressing medicines, creating a need for improved anti-tussive therapies. Most patients with chronic cough also display heightened sensitivity such that they experience a persistent sense of the need to cough and often innocuous stimuli can trigger their coughing. This hypersensitivity underpins the newly described concept of Cough Hypersensitivity Syndrome (CHS), a term that encapsulates the notion of common underlying mechanisms producing neuronal activation, sensitization and/or dysfunction, which are at the core of excessive coughing. Understanding these mechanisms has been a focus of recent research efforts in the field in the hope that new therapies can be developed to selectively target sensitized unproductive cough whilst maintaining the reflexive cough essential for airway protection. However, efforts to achieve this have been slower than expected, in part because of some significant challenges and limitations translating current cough models. In this review, we will summarize recent advances in our understanding of the sensory circuits innervating the respiratory system important for cough, how cough sensory pathways become hypersensitive, and some of the recently described neural targets under development for treating chronic coughing. We will present the case that better use of current cough models and/ or the development of new models is ultimately needed to advance our efforts to translate the discovery of basic cough mechanisms into effective medicines for treating patients with chronic cough.

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  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543