Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship

Research priorities in prehabilitation for patients undergoing cancer surgery: an international Delphi study

Background Recently, the number of prehabilitation trials has increased significantly. The identification of key research priorities is vital in guiding future research directions. Thus, the aim of this collaborative study was to define key research priorities in prehabilitation for patients undergoing cancer surgery. Methods The Delphi methodology was implemented over three rounds of surveys distributed to prehabilitation experts from across multiple specialties, tumour streams and countries via a secure online platform. In the first round, participants were asked to provide baseline demographics and to identify five top prehabilitation research priorities. In successive rounds, participants were asked to rank research priorities on a 5-point Likert scale. Consensus was considered if > 70% of participants indicated agreement on each research priority. Results A total of 165 prehabilitation experts participated, including medical doctors, physiotherapists, dieticians, nurses, and academics across four continents. The first round identified 446 research priorities, collated within 75 unique research questions. Over two successive rounds, a list of 10 research priorities reached international consensus of importance. These included the efficacy of prehabilitation on varied postoperative outcomes, benefit to specific patient groups, ideal programme composition, cost efficacy, enhancing compliance and adherence, effect during neoadjuvant therapies, and modes of delivery. Conclusions This collaborative international study identified the top 10 research priorities in prehabilitation for patients undergoing cancer surgery. The identified priorities inform research strategies, provide future directions for prehabilitation research, support resource allocation and enhance the prehabilitation evidence base in cancer patients undergoing surgery

Effects of high intensity interval training on exercise capacity in people with chronic pulmonary conditions: a narrative review

Background: Exercise training is important in the management of adults with chronic pulmonary conditions. However, achieving high intensity exercise may be challenging for this clinical population. There has been clinical interest in applying interval-based training as a strategy to optimise the load that can be tolerated during exercise training. Evidence for such an approach is limited in most chronic pulmonary populations. Main body: In this narrative review, we provide an appraisal of studies investigating whole-body high intensity interval training (HIIT) in adults with chronic obstructive pulmonary disease (COPD). This is the first review to also include studies investigating HIIT in people with conditions other than COPD. Studies undertaken in adults with a chronic pulmonary condition were reviewed when participants were randomised to receive; (i) HIIT or no exercise or, (ii) HIIT or moderate intensity continuous exercise. Data were extracted on peak rate of oxygen uptake (VO2peak; 'cardiorespiratory fitness') and maximal work rate (Wmax; 'exercise capacity').In people with COPD, two studies demonstrated between-group differences favouring HIIT compared with no exercise. There appears to be no advantage for HIIT compared to continuous exercise on these outcomes. In people with cystic fibrosis (CF), no studies have compared HIIT to no exercise and the two studies that compared HIIT to continuous exercise reported similar benefits. In people prior to resection for non-small cell lung cancer, one study demonstrated a between-group difference in favour of HIIT compared with no exercise on VO2peak. In people with asthma, one study demonstrated a between-group difference in favour of HIIT compared with no exercise on VO2peak and one that compared HIIT to continuous exercise reported similar benefits. No studies were identified non-CF bronchiectasis or interstitial lung diseases. Conclusions: High intensity interval training increases cardiorespiratory fitness and exercise capacity when compared with no exercise and produces a similar magnitude of change as continuous exercise in people with COPD. There is a paucity of studies exploring the effects of HIIT in other chronic pulmonary conditions

High-Intensity Interval Training Is Effective at Increasing Exercise Endurance Capacity and Is Well Tolerated by Adults with Cystic Fibrosis

BACKGROUND: To optimize outcomes in people with cystic fibrosis (CF), guidelines recommend 30 to 60 min of moderate-intensity aerobic exercise on most days. Accumulating this volume of exercise contributes importantly to the substantial treatment burden associated with CF. Therefore, the main aim of this study was to investigate the effects of low-volume high-intensity interval training (HIIT) on exercise capacity in people with CF. METHODS: This randomized controlled trial included people with CF aged ≥15 years, who were allocated to either eight weeks of thrice-weekly 10-min sessions of HIIT (experimental group) or eight weeks of weekly contact (control group). Before and after the intervention period, participants completed measurements of time to symptom limitation (Tlim) during a constant work rate cycle ergometry test (primary outcome), and maximal work rate (Wmax) during a ramp-based cycle ergometry test and health-related quality of life (HRQoL). RESULTS: Fourteen participants (median (IQR) age 31 (28, 35) years, forced expiratory volume in 1 second (FEV1) 61 (45, 80) % predicted) were included (seven in each group). Compared to the control group, participants in the experimental group demonstrated a greater magnitude of change in Tlim, Wmax (p = 0.017 for both) and in the physical function domain of HRQoL (p = 0.03). No other between-group differences were demonstrated. Mild post-exercise muscle soreness was reported on a single occasion by four participants. Overall, participants attended 93% of all HIIT sessions. DISCUSSION: Eight weeks of low-volume (i.e., 30-min/week) HIIT produced gains in exercise capacity and self-reported physical function and was well tolerated by people with CF

Efeitos do apoio dos membros superiores sobre a força muscular respiratória e função pulmonar de doentes com doença pulmonar obstrutiva crónica

Resumo: Objetivo: Analisar o efeito do apoio de membros superiores sobre a força muscular respiratória e função pulmonar de pacientes com Doença Pulmonar Obstrutiva Crónica (DPOC). Métodos: Vinte pacientes com DPOC (11 homens) com idade de 67 ± 8 anos e IMC 24 ± 3 Kg · mâ2, foram submetidos a avaliações de Pressão Inspiratória e Expiratória Máximas (PImax e PEmax, respectivamente) e espirometria com e sem apoio dos membros superiores em ordem aleatória. A avaliação com apoio dos membros superiores foi realizada em posição ortostática, com o apoio dos membros superiores na altura do processo estilóide da ulna, flexão de cotovelos e tronco inclinado à frente, ambos em aproximadamente 30 graus, de modo a promover descarga de peso em membros superiores. A avaliação sem apoio de membros superiores foi realizada também em posição ortostática, porém com os membros superiores relaxados ao lado do corpo. O intervalo entre as avaliações foi de uma semana. Resultados: A PImax, PEmax e Ventilação Voluntária Máxima (VVM) foram maiores com a utilização do apoio do que sem o apoio (PImax 64 ± 22 cmH2O versus 54 ± 24 cmH2O, p = 0,00001; PEmax 104 ± 37 cmH2O versus 92 ± 37 cmH2O, p = 0,00001 e VVM 42 ± 20 L/min versus 38 ± 20 L/min, p = 0,003). As demais variáveis não apresentaram diferenças estatisticamente significativas. Conclusão: O apoio de membros superiores resultou em maior capacidade de gerar força e endurance dos músculos respiratórios em pacientes com DPOC. Abstract: Objective: To analyze the effect of arm bracing posture on respiratory muscle strength and pulmonary function in patients with Chronic Obstructive Pulmonary Disease (COPD). Methods: 20 patients with COPD (11 male; 67 ± 8 years; BMI 24 ± 3 Kg · mâ2) were submitted to assessments of Maximal Inspiratory and Expiratory Pressures (MIP and MEP, respectively) and spirometry with and without arm bracing in a random order. The assessment with arm bracing was done on standing position and the height of the support was adjusted at the level of the ulnar styloid process with elbow flexion and trunk anterior inclination of 30 degrees promoting weight discharge in the upper limbs. Assessment without arm bracing was also performed on standing position, however with the arms relaxed alongside the body. The time interval between assessments was one week. Results: MIP, MEP and maximal voluntary ventilation (MVV) were higher with arm bracing than without arm bracing (MIP 64 ± 22 cmH2O versus 54 ± 24 cmH2O, p = 0,00001; MEP 104 ± 37 cmH2O versus 92 ± 37 cmH2O, p = 0,00001 and MVV 42 ± 20 L/min versus 38 ± 20 L/min, p = 0,003). Other variables did not show statistical signifi cant difference. Conclusion: The arm bracing posture resulted in higher capacity to generate force and endurance of the respiratory muscles in patients with COPD. PALAVRAS-CHAVE: Extremidade superior, Músculos respiratórios, Espirometria, Doença Pulmonar Obstrutiva Crónica, KEYWORDS: Upper limb, Respiratory muscles, Pulmonary function test, Chronic Obstructive Pulmonary Diseas

Efeitos do apoio dos membros superiores sobre a força muscular respiratória e função pulmonar de pacientes com doença pulmonar obstrutiva crônica

Objective: To analyze the effect of arm bracing posture on respiratory muscle strength and pulmonary function in patients with Chronic Obstructive Pulmonary Disease (COPD).Methods: 20 patients with COPD (11 male; 67 +/- 8 years; BMI 24 +/- 3 Kg . m(-2)) were submitted to assessments of Maximal Inspiratory and Expiratory Pressures (MIP and MEP, respectively) and spirometry with and without arm bracing in a random order. The assessment with arm bracing was done on standing position and the height of the support was adjusted at the level of the ulnar styloid process with elbow flexion and trunk anterior inclination of 30 degrees promoting weight discharge in the upper limbs. Assessment without arm bracing was also performed on standing position, however with the arms relaxed alongside the body. The time interval between assessments was one week.Results: MIP, MEP and maximal voluntary ventilation (MW) were higher with arm bracing than without arm bracing (MIP 64 +/- 22 cmH(2)O versus 54 +/- 24 cmH(2)O, p = 0,00001; MEP 104 +/- 37 cmH(2)O versus 92 +/- 37 cmH(2)O, p = 0,00001 and MW 42 +/- 20 L/min versus 38 +/- 20 L/min, p = 0,003). Other variables did not show statistical significant difference.Conclusion: The arm bracing posture resulted in higher capacity to generate force and endurance of the respiratory muscles in patients with COPD. (C) 2009 Published by Elsevier Espana, S.L. on behalf of Sociedade Portuguesa de Pneumologia. All rights reserved

Efeito imediato e a curto prazo do cigarro sobre o transporte mucociliar nasal de fumadores

ResumoIntrodução e objectivoA eficiência do transporte mucociliar pode variar em diferentes condições, como na exposição a partículas nocivas do fumo do cigarro. O presente estudo avaliou os efeitos do cigarro, tanto imediato quanto a curto prazo, no transporte mucociliar nasal de fumadores por meio da quantificação do tempo de trânsito da sacarina (TTS), e correlacionou-os com a intensidade de consumo tabagístico.MétodosDezanove fumadores ativos (11 homens; 51±16 anos; IMC 23±9kg/m2; 27±11 cigarros/dia; 44±25 anos/maço), participantes de programa de intervenção antitabagismo, responderam a um questionário referente ao histórico tabagístico e foram submetidos à avaliação da função pulmonar (espirometria) e transporte mucociliar (pelo TTS), este imediatamente e após 8 horas do acto de fumar. Para comparação, um grupo pareado composto por 19 indivíduos saudáveis não fumadores foi avaliado por meio dos mesmos testes.ResultadosQuando comparados ao TTS de não fumadores (10±4min; média±desvio padrão), os fumadores apresentaram tempo de transporte similar imediatamente após fumar (11±6min; p=0,87) e significativamente mais lento 8 horas após fumar (16±6min; p=0,005 versus não fumadores e p=0,003 versus fumadores). Em fumadores, o TTS 8 horas após fumar correlacionou-se positivamente com a idade (r=0,59; p=0,007), o número de cigarros/dia (r=0,53; p=0,02) e o índice anos/maço (r=0,74; p=0,0003).ConclusãoEmbora indivíduos fumadores imediatamente após fumar apresentem transporte mucociliar similar ao de indivíduos não fumadores, 8 horas após o consumo tabagístico o transporte mucociliar mostra-se reduzido e relacionado com hábitos tabagísticos.AbstractBackground and objectivesThe efficiency of mucociliary transport may vary in different conditions, such as in exposure to harmful particles of the cigarette smoke. The present study evaluated the acute and short term effects of smoking on nasal mucociliary clearance in current smokers by the quantification of the Saccharin Transit Time (STT), and to investigate its correlation with the history of tobacco consumption.MethodsNineteen current smokers (11 men, 51±16years; BMI 23±9kg/m2, 27±11 cigarettes per day, 44±25 pack-years), entering a smoking cessation intervention program, responded to a questionnaire concerning smoking history and were submitted to lung function assessment (spirometry) and the STT test. STT was assessed immediately after smoking and 8hours after smoking. The STT test was also performed in nineteen matched healthy non-smokers’ who served as control group.ResultsWhen compared to STT in non-smokers’ (10±4min; mean±standard deviation), smokers presented similar STT immediately after smoking (11±6min; p=0.87) and slower STT 8hours after smoking (16±6min; p=0.005 versus non-smokers’ and p=0.003 versus immediately after smoking). STT 8hours after smoking correlated positively with age (r=0.59; p=0.007), cigarettes per day (r=0.53; p=0.02) and pack-years index (r=0.74; p=0.0003).ConclusionsIn smokers, although the mucociliary clearance immediately after smoking is similar to non-smokers’, eight hours after smoking it is reduced, and this reduction is closely related to the smoking habits