The Year in Review 2016


We are pleased to bring you the following journal review, part of a project developed by the ITS SpR

Educational Officer Dr Robert Smyth.


Top Reads for 2016

By Dr Waheed Shah, SpR in Respiratory Medicine


Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

McGeachie MJ, Yates KP, Zhou X, Guo F, Sternberg AL, Van Natta ML, Wise RA, Szefler SJ, Sharma S, Kho AT, Cho MH, Croteau-Chonka DC, Castaldi PJ, Jain G,

Sanyal A, Zhan Y, Lajoie BR, Dekker J, Stamatoyannopoulos J, Covar RA, Zeiger RS, Adkinson NF, Williams PV, Kelly HW, Grasemann H, Vonk JM, Koppelman GH, Postma DS, Raby BA, Houston I, Lu Q, Fuhlbrigge AL, Tantisira KG, Silverman EK, Tonascia J, Weiss ST, Strunk RC; CAMP Research Group.

N Engl J Med. 2016 May 12

Children with asthma are a population at risk of chronic airflow limitation in later life. It is thought that patterns of growth and early decline in FEV1 up to late adolescence are an important determinant of lung function in adulthood. To further investigate this relationship the authors performed a retrospective review of 13 years of annual spirometry data from children aged 5-12 years with persistent mild-moderate asthma, and who had at least one measurement at ≥23 years of age. Measurements were compared to longitudinal spirometry data from the general population. 684 patients with 15,798 spirometric measurements were assessed. 75% of the participants had abnormal patterns of lung growth and decline in early adulthood. Low FEV1 at baseline [OR 0.86, (p<0.001) per 1% change from predicted] and male gender (OR 8.18 p<0.001) were the most significant predictors of abnormal longitudinal patterns of lung function growth and decline. 11% of the cohort met the spirometric criteria for COPD by age 30.

FINAL STATEMENT: Although causality was not established, this study strongly supports the hypothesis that both reduced growth and early decline in FEV1 predict the asthma-COPD overlap syndrome in adult patients with a history of mild-moderate childhood asthma.


Effect of the continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis.

Nathan SD, Albera C, Bradford WZ, Costabel U, du Bois RM, Fagan EA, Fishman RS, Glaspole I, Glassberg MK, Glasscock KF, King TE Jr, Lancaster L, Lederer

DJ, Lin Z, Pereira CA, Swigris JJ, Valeyre D, Noble PW, Wells AU.

Thorax. 2016 May;71(5):429-35

The clinical course of patients with a diagnosis of IPF remains elusive with decline in FVC being an independent predictor of mortality. This post hoc exploratory analysis examined the effect of continued treatment with pirfenidone vs placebo in a population of patients who had a decline in their FVC of ≥10% in the first 6 months of treatment. Data from 1247 patients recruited to the ASCEND and CAPACITY trials was analysed. 34 (5.5%) and 68 (10.9%) patients in the pirfenidone and placebo groups respectively met the criteria for decline in FVC of > 10% in the first 6 months. Fewer patients in the pirfenidone group showed a further decline in FVC compared to the placebo group (5.9% vs 27.9%; (p=0.009). The median change in %FVC was 2.1% (−10.6, 16.2) and −3.0% (−59.1, 13.0) in the pirfenidone and placebo groups respectively (p=0.154). There was one death (2.9%) in the treatment group and 14 (20.6%) in the placebo group (p= 0.018).

FINAL STATEMENT: Although the assessment of the therapeutic response to pirfenidone is complicated by a substantial degree of intrasubject variability in FVC changes, this analysis suggests that the continuation of pirfenidone is associated with a significantly reduced decline in FVC and death compared to placebo.



Pregabalin and Speech Pathology Combination Therapy for Refractory Chronic Cough.

Vertigan AE, Kapela SL, Ryan NM, Birring SS, McElduff P, Gibson PG.

CHEST 2016; 149(3): 639-648

Speech pathology treatment (SPT) has been shown to improve symptoms in chronic refractory cough (CRC). This randomised double blind placebo controlled trial tested the hypothesis that combined SPT and pregabalin pharmacotherapy would have a superior outcome to SPT alone. A total of 40 patients with CRC were recruited and randomised with equal allocation to SPT plus pregablin 300mg daily or SPT plus placebo. Differences in cough frequency using the Leicester cough monitor, cough severity using a visual analog scale (cough VAS) and cough related quality of life using the Leicester cough questionnaire (LCQ) were the primary outcome measures. The treatment cohort showed a greater degree of improvement in LCQ and cough VAS than SPT plus placebo. The mean difference in LCQ was 3.5, 95% CI of difference 1.1- 5.8 (p=0.024). The median difference in cough VAS was 25.1, 95% CI of difference 10.6-39.6 (p=.002). Cough frequency reduced significantly in both groups without a statistically significant difference between them. Median capsaicin cough sensitivity improved from 15.7 to 47.5μM in treatment group and from 3.92 to 15.7μM with CPT alone.

FINAL STATEMENT: Although a small study, this trial provides valuable evidence for the efficacy of pregabalin in the management of CRC, a common and difficult condition for respiratory physicians to manage.



Short-term and long-term response to pulmonary exacerbation treatment in cystic fibrosis.

Heltshe SL, Goss CH, Thompson V, Sagel SD, Sanders DB, Marshall BC, Flume PA.

Thorax 2016; Mar; 71:223-229

There is no general consensus on the treatment of pulmonary exacerbations (PEx) in patients with cystic fibrosis (CF) and therefore management practice varies widely. This observational prospective multi-centre study analysed the treatment of patients with CF > 10 years of age and PEx. The aim of the trial was to correlate the heterogeneity of care in PEx with measures of clinical response, including changes in symptom severity score short and long term changes in spirometry, and the period of time to the next exacerbation. A total of 123 patients (60.2%, aged 23.1 +10.2 years) were treated with 2 or more intravenous antibiotics for a clinically diagnosed PEx. 33% of patients had a < 10% relative improvement in FEV1 during treatment. This was associated with a failure to recover to baseline lung function at 3 months post treatment [OR = 7.8, 95% CI 1.9-31.6, (p= 0.04)] and a longer time to next intravenous antibiotic [HR =0.48,95% CI 0.27 to 0.85, (p =0.011)]. Symptom improvement was not associated with subsequent lung function or time to next antibiotic treatment.

FINAL STATEMENT: A lack of improvement in FEV1 during treatment for a PEx appears to be associated with a failure to recover to baseline lung function. This may allow us to identify patients in need of more intensive treatment and closer follow up.


Airway microbiota determines innate cell inflammatory or tissue remodeling profiles in lung transplantation.

Bernasconi E, Pattaroni C, Koutsokera A, Pison C, Kessler R, Benden C, Soccal PM, Magnan A, Aubert JD, Marsland BJ, Nicod LP; SysCLAD Consortium.

Am J Respir Crit Care Med. 2016 Jun 1 

In lung transplant recipients, the mechanism underlying graft survival versus chronic lung allograft dysfunction (CLAD) is largely unknown. Microbial dysbiosis (imbalance) has been discovered in lung disease and there is data to suggest host-microbe interactions have functional effects on the airway. This study sought to assess whether host-microbe interactions determine airway immunological tone in the transplanted lung. 203 BAL samples in 112 post transplant patients were collected, with

isolation of microbiota DNA, and total RNA for the selection of gene expression profiles involved in activating macrophages. On the basis of this analysis, 3 sample profiles were identified, pro-remodelling (46.6%), intermediate (40.3%) and pro-inflammatory (13.1%). The highest prevalence of the pro-inflammatory and remodelling profiles was associated with microbial dysbiosis. Conversely an intermediate activation profile was maximal in those with no microbial imbalance. Analysis of bacterial exposures to THP-1 derived macrophages (surrogate cells for lung transplant recipient alveolar macrophages) replicated these findings in vitro, with infectious communities being pro-inflammatory and Prevotella communities being pro-remodelling. 

FINAL STATEMENT: This study provides a first mechanistic insight into the importance of airway microbial balance and its interactions with immune cell activation states in lung transplant patients.