Defining Resilience to Smoking-related Lung Disease: A Modified Delphi Approach from SPIROMICS.

Rationale: Diagnosis of chronic obstructive pulmonary disease (COPD) relies on abnormal spirometry. However, spirometry may underestimate the effects of smoking, missing smokers with respiratory disease who have minimal or no airflow obstruction. Objectives: To develop a multidimensional definition of a lung-related "resilient smoker" that is useful in research studies and then identify a resilient smoker subgroup in the SPIROMICS (SubPopulations and InteRmediate Outcome Measures In COPD Study) cohort using this definition. Methods: We performed a three-round modified Delphi survey among a panel of COPD experts to identify and reach a consensus on clinical and radiographic domains to be included in a lung-related resilient smoker definition. Consensus on domains of resilience was defined as ⩾80% of experts voting "agree" or "strongly agree" on a 5-point Likert scale. The Delphi-derived definition of resilience was applied to SPIROMICS to identify resilient smokers, whom we then characterized using known biomarkers of COPD. Results: Consensus was achieved on 6 of 12 diagnostic items, which include cough and sputum production, dyspnea, radiographic measures of emphysema and small airways disease, exacerbations, and decline in forced expiratory volume in 1 second. Although 892 SPIROMICS participants were classified as smokers with preserved lung function by spirometry, only 149 participants (16.7%) qualified as resilient smokers by our definition. Blood biomarker expression of CRP (C-reactive protein) and sTNFRSF1A (soluble tumor necrosis receptor factor1A) was lower in resilient than nonresilient smokers (P = 0.02 and P = 0.03). Conclusions: A Delphi-derived consensus definition of resilient smoker identified 83.3% of smokers with preserved spirometry as "nonresilient" based on the presence of adverse effects of smoking on the lung. Resilient smokers were biologically distinct from nonresilient smokers based on CRP measurements. Clinical trial registered with ClinicalTrials.gov (NCT01969344).

Prospective, randomized, controlled trial using best-selling smoking-cessation book.

Our prospective, randomized, controlled trial aimed to evaluate the efficacy of the self-help book, The Easy Way to Stop Smoking, by Allen Carr, in promoting smoking cessation in patients with head and neck cancer. We assessed active smokers for their willingness to read a smoking cessation book. Participants were randomized to either receive the book from our department or recommended to purchase the book. All patients received smoking cessation counseling at recruitment. Phone surveys were conducted at short- and long-term intervals to determine if the patients had purchased and/or read the book and whether they were still smoking. One hundred twelve patients were recruited, 52 of whom completed follow-up surveys. Those who received the book for free were more likely to read the book (p = 0.05). Reading the book did not correlate with successful smoking cessation (p = 0.81). Some 26% of the 27 patients who received the book quit smoking compared with 32% of the 25 patients who were recommended the book (p = 0.76). Patients who indicated motivation to quit smoking were more likely to succeed. In our study, smoking cessation did not appear to be influenced by reading The Easy Way to Stop Smoking. Despite 80.8% of the cohort indicating at least a readiness to quit smoking at recruitment, only 28.8% of patients managed to achieve successful smoking cessation at long-term follow-up. Patient motivation remains an important factor in achieving long-term smoking abstinence. Quitting smoking remains a daunting challenge for patients, with multiple interventions likely needed to achieve cessation.

Flow Decay: A Novel Spirometric Index to Quantify Dynamic Airway Resistance.

BACKGROUND: Dynamic airway resistance from obstructive disease causes a concavity in the mid-expiratory portion of the spirometric flow-volume loop. We developed a simple model to measure the exponential decay in air flow during forced exhalation to quantify the extent of dynamic airway obstruction and facilitate the detection of obstructive airway diseases clinically. METHODS: We calculated flow decay as the slope of volume versus ln(1/flow) in mid-exhalation. We derived the normal range in a derivation group of healthy volunteers in whom spirometry had been performed repeatedly. We validated the derived upper limit of normal (mean + 2 × SD) by using it to distinguish a separate group of healthy subjects (n = 25) from subjects with independently diagnosed reversible airway obstruction (n = 31) and subjects with obstruction, hyperinflation, and air trapping (n = 62). RESULTS: In the derivation group (n = 7), the mean ± SD flow decay was 0.588 ± 0.107 L-1 (upper limit of normal = 0.802 L-1). Flow decay in 23 of 25 healthy subjects in the validation group was below the upper limit of normal. In contrast, it was above the upper limit of normal in 29 of 31 subjects with reversible airway obstruction (sensitivity 94%, 95% CI 79-99%; specificity 92%, 95% CI 74-99%) and in 59 of 62 of subjects with obstruction, hyperinflation, and air trapping (sensitivity 92%, 95% CI 74-99%; specificity 95%, 95% CI 86-99%). CONCLUSIONS: Flow decay distinguished subjects with obstructive lung defects from healthy subjects. It is a straightforward representation of spirometry data that provides a reproducible index to quantify dynamic airway obstruction.

IFN-gamma production during initial infection determines the outcome of reinfection with respiratory syncytial virus.

RATIONALE: Severe respiratory syncytial virus (RSV) bronchiolitis has been associated with deficient IFN-gamma production in humans, but the role of this cytokine in determining the outcome of reinfection is unknown. OBJECTIVES: To define the role of IFN-gamma in the development of RSV-mediated airway hyperresponsiveness (AHR) and lung histopathology in mice. METHODS: Wild-type (WT) and IFN-gamma knockout mice were infected with RSV in the newborn or weaning stages and reinfected 5 weeks later. Airway responses were assessed on Day 6 after the primary or secondary infection. MEASUREMENTS AND MAIN RESULTS: Both WT and IFN-gamma knockout mice developed similar levels of AHR and airway inflammation after primary infection. After reinfection, IFN-gamma knockout mice, but not WT mice, developed AHR, airway eosinophilia, and mucus hyperproduction. Intranasal administration of IFN-gamma during primary infection but not during reinfection prevented the development of these altered airway responses on reinfection in IFN-gamma knockout mice. Adoptive transfer of WT T cells into IFN-gamma knockout mice before primary infection restored IFN-gamma production in the lungs and prevented the development of altered airway responses on reinfection. Treatment of mice with IFN-gamma during primary neonatal infection prevented the enhancement of AHR and the development of airway eosinophilia and mucus hyperproduction on reinfection. CONCLUSIONS: IFN-gamma production during primary RSV infection is critical to the development of protection against AHR and lung histopathology on reinfection. Provision of IFN-gamma during primary infection in infancy may be a potential therapeutic approach to alter the course of RSV-mediated long-term sequelae.