Based on their findings from a prospective, randomized, controlled equivalence trial, Holland and colleagues conclude that a 8-week home- based rehabilitation model produced short-term clinical outcomes that were equivalent to a center-based pulmonary rehabilitation program.[1] To their credit, the authors' recruitment and statistical design were of high quality, as were the outcome measures used. We acknowledge that the home-based model with exercise training and education on self-management partially fits with the needs of patients with COPD who are unable and/or reluctant to attend a formal hospital-based pulmonary rehabilitation program.[2, 3] Then again, we believe that some issues need additional discussion. First, the home-based intervention as studied by Holland and colleagues used only unsupervised exercise training and education; other core components of pulmonary rehabilitation, like occupational therapy, nutritional modulation, and psychological counseling were lacking.[4] Therefore, needs and extra-pulmonary features of individual patients, such as symptoms of anxiety and depression (present in one-fifth of the current study sample), an abnormal body composition (in the current study sample about two-thirds of the patients were overweight or obese) and/or other medical comorbidities (one-fifth of the current sample had 4 or more reported comorbidities) cannot adequately be dealt with during a home- based intervention. Moreover, as patients experience a complex health behavior change process during pulmonary rehabilitation, we should not underestimate the major contributing role of skilled healthcare professionals that are part of the dedicated pulmonary rehabilitation team.[5] Therefore, the call from ATS/ERS[2] to increase the financial support of existing comprehensive hospital-based pulmonary rehabilitation programs is still very valid. This also applies to the call to start new programs, which will reduce the time and distance to travel from home to hospital. Moreover, this approach also takes into consideration the desire to exercise within a peer group together with the possibility for social interaction.[6] Remarkably, 54 patients (80% of the patients who did not consent) did not volunteer to participate in this RCT as they wanted to undertake rehabilitation in a hospital-based program. Indeed, the patients that volunteered to participate in the study of Holland and colleagues were all on the waiting list for a hospital-based pulmonary rehabilitation program. Whether and to what extent home-based exercise interventions are safe, feasible and effective in complex patients with COPD remains unanswered. As the complexity of COPD patients increases, also the complexity of rehabilitative interventions needs to increase. For example, patients with chronic respiratory failure may need supervised exercise training with non -invasive ventilation; in severely underweight patients close supervision and interaction between physiotherapist and dietician is required to avoid further weight loss during rehabilitation; smoking cessation programs are an important integrated part of rehabilitation; subjects with frequent exacerbations or recovering from a severe exacerbation requiring hospitalization need close monitoring. Indeed, Greening and colleagues already showed that an early, unsupervised, home-based exercise training program is not the right care at the right time at the right place for patients with chronic respiratory disease recovering from an acute hospital admission.[7] Interestingly, patients included in the hospital-based rehabilitation group only attended 8 of the 16 scheduled sessions (range 0-16). Half of the patients did not qualify as a program completer, defined as undertaking 70% of the planned sessions. This may, at least in part, explain the disappointing mean improvements in exercise capacity and disease-specific quality of life. The authors reason that the presence of medical comorbidities may be one of the main reasons for the low completion rate. Nevertheless, our group[8] and others[9] have shown that multimorbid COPD patients can complete a multidisciplinary hospital-based pulmonary rehabilitation program and can achieve clinically relevant improvements in exercise capacity and health status. The external validity of the current findings for patients with long-term oxygen therapy (LTOT) and/or very severe dyspnea is limited, as less than 5% of the patients were LTOT users and/or scored grade 4 on the modified Medical Research Council dyspnea scale. Towards the future, we all recognize the need to increase the implementation, utilization and delivery of pulmonary rehabilitation.[2] There are numerous possible solutions, including, but not limited to 1) formal training of healthcare professionals in the science, process and benefits of pulmonary rehabilitation; 2) increase payer awareness and knowledge of pulmonary rehabilitation; 3) increase patient awareness and knowledge of pulmonary rehabilitation; 4) to improve patients access to pulmonary rehabilitation by augmenting program commissioning through increased sustainable payer funding, and creating new programs in geographical areas where demand exceeds capacity; and 5) developing and investigating novel program models that will make pulmonary rehabilitation more accessible to patients.[2] The home-based approach fits with the last mentioned possible solution. Then again, it seems reasonable to state that a hospital-based integrated program with a skilled and dedicated interdisciplinary pulmonary rehabilitation team may be more suitable for COPD patients who truly need a comprehensive program due to their severely impaired pulmonary function, numerous extra-pulmonary features and/or medical comorbidities than a home-based model. Embracing the principles of P4 medicine (e.g., the right patient, for the right treatment, for the right dose, for the right outcome), we must consider that pulmonary rehabilitation programs need to evolve towards personalized medicine, or precision rehabilitation programs, including the right setting for the intervention. An integrated assessment of the patient's physical, psychological, and social complexities, will provide us with the necessary information about which approach is most feasible and effective for the individual patient with COPD.

References

1. Holland, A.E., et al., Home-based rehabilitation for COPD using minimal resources: a randomised, controlled equivalence trial. Thorax, 2016.

2. Rochester, C.L., et al., An Official American Thoracic Society/European Respiratory Society Policy Statement: Enhancing Implementation, Use, and Delivery of Pulmonary Rehabilitation. Am J Respir Crit Care Med, 2015. 192(11): p. 1373-86.

3. Spruit, M.A., et al., Differences in content and organisational aspects of pulmonary rehabilitation programmes. Eur Respir J, 2014. 43(5): p. 1326-37.

4. Spruit MA, S.S., Garvey C, et al, American Thoracic Society/European Respiratory Society statement on pulmonary rehabilitation. American journal of respiratory and critical care medicine, 2013. in press.

5. Meis, J.J., et al., A qualitative assessment of COPD patients' experiences of pulmonary rehabilitation and guidance by healthcare professionals. Respir Med, 2014. 108(3): p. 500-10.

6. Hogg, L., et al., People with COPD perceive ongoing, structured and socially supportive exercise opportunities to be important for maintaining an active lifestyle following pulmonary rehabilitation: a qualitative study. J Physiother, 2012. 58(3): p. 189-95.

7. Greening, N.J., et al., An early rehabilitation intervention to enhance recovery during hospital admission for an exacerbation of chronic respiratory disease: randomised controlled trial. BMJ, 2014. 349: p. g4315.

8. Mesquita, R., et al., Objectively identified comorbidities in chronic obstructive pulmonary disease: impact on pulmonary rehabilitation outcomes. Eur Respir J, 2015.

9. Crisafulli, E., et al., Role of comorbidities in a cohort of patients with COPD undergoing pulmonary rehabilitation. Thorax, 2008. 63(6): p. 487-92.

Conflict of Interest:

None declared

Dear Editor,

with the greatest interest I have read the publication "Lung function and airway obstruction: associations with circulating markers of cardiac function and incident heart failure in older men--the British Regional Heart Study" by Wannamethee et al. (Thorax 2016 71:526-534). Analyzing a large database with 13 years of prospective follow up the authors conclude that "reduced FEV1 reflecting airflow obstruction is associated with cardiac dysfunction and increased risk of incident HF". Concerning the underlying pathophysiology the authors discussed "Airway obstruction decreases expiratory flow rates and causes lung hyperinflation, which is associated with decreased cardiac function and may increase NT-proBNP.". While this is certainly appealing and grounded on previous publications, the concept of neurohumoral activation might contribute to the observed findings.

With a variety of methods we and others described striking neurohumoral activation in patients with COPD (1) (2) (3). From patients with heart failure it is well known, that neurohumoral activation is central in the pathophysiology of this disease (4). Indeed, ? blocker and angiotensin receptor blocker reduce mortality and morbidity by their impact on sympathetic and neurohumoral activation in heart failure (4). Thus it is intriguing to speculate that airway obstruction in COPD aggravates heart failure by sympathetic activation.

Yours sincerely Stefan Andreas

References 1. Andreas S, Anker SD, Scanlon PD, Somers VK. Neurohumoral activation as a link to systemic manifestation of chronic lung disease. Chest 2005; 128: 3618-3624. 2. Raupach T, Bahr F, Herrmann P, Luethje L, Heusser K, Hasenfuss G, Bernardi L, Andreas S. Slow breathing reduces sympathoexcitation in COPD. Eur Respir J 2008; 32: 387-392. 3. Luthje L, Raupach T, Michels H, Unsold B, Hasenfuss G, Kogler H, Andreas S. Exercise intolerance and systemic manifestations of pulmonary emphysema in a mouse model. Respiratory research 2009; 10: 7. 4. Schrier RW, Abraham WT. Hormones and hemodynamics in heart failure. The New England journal of medicine 1999; 341: 577-585.

Conflict of Interest:

None declared

Dear Editor,

I read with interest the paper by Alfageme and colleagues (1) who investigated the efficacy of anti-pneumococcal vaccination in patients with COPD. To have new data in an area which has suffered from a surfeit of meta-analysis and even analysis of the meta-analysis is good and their results are quite clear. Although they do not specifically comment I presume that their primary end point was accumulative proportion of patients without pneumonia during the follow up period. There is no significant effect. Unfortunately, this clear result is then muddied by data dredging. Small subgroups of patients, those under 65 and those with severe COPD are extracted from the data and unsurprisingly are found to be significantly improved. The reliability of this reanalysis is at best dubious and probably should be reserved for building hypotheses to be tested in subsequent studies.

Where then does this leave the costly vaccination programme recommended by NICE? It should be urgently reconsidered, particularly as the reanalysis produced by Alfageme and colleagues suggest that the patients targeted by this programme, those over 65 years of age, may actually be harmed with 14% greater incidence of pneumonia in the active treatment group. Whilst statistically insignificant how can the national guidelines, which are supposed to be evidence based, fly in the face of such new evidence?

PROFESSOR ALYN H MORICE
Professor of Respiratory Medicine
Head of Division of Academic Medicine

References

1. Alfageme I, Vazquez R, Reyes N, et al. Clinical efficacy of anti- pneumococcal vaccination in patients with COPD. Thorax 2006;61:189-195.

Dear Editor,

We would like to comment to the limitations of the Christopher-study (JAMA 2006;295) mentioned by Dr. Bari. He states that “the limitations of this study include the use of two different kinds of CT scanner (multi- detector and single-detector) with potentially different pick up rates”. The other limitation stated is: “the prevalence of PE of 23.2% in the ‘clinically unlikely PE and abnormal D-dimer’ group shows that a clinical scoring system alone is inadequate”.

It is commonly suggested that multi-detector row CT is more likely to detect subsegmental PE in comparison to single-detector row CT. However, whether subsegmental PE is clinically relevant and needs to be treated with anticoagulants is uncertain(Eyer, Am J Roentgenol 2005;184, Goodman, Radiology 2005;234). Because we used multi-detector row CT, there’s a potential for overdiagnosis of subsegmental PE that are not clinically important. The limitation of our study was that patients did not undergo confirmatory pulmonary angiography and thus, our study design did not permit assessing the rate of false-positive CT-scans. Because only 10% of patients underwent single-detector row CT, a meaningful comparison of both techniques was not possible. However, as we have mentioned in the discussion section, the prevalence of PE in our study (20%) compares well with the prevalence of PE in a previous study (24%, van Strijen, Ann Int Med 2003;138) that used solely single-detector row CT and does not support a concern that multi-detector row CT leads to a high number of overdiagnosis of subsegmental PE.

Concerning the other limitation mentioned by Bari, we think that a clinical scoring system is not designed to adequately diagnose PE, but to categorize patients into groups with low and high risks of PE. The clinical scoring system we used, showed that patients categorized as ‘PE unlikely’ can be safely left untreated if the D-dimer test is normal. In this way, we were able to prevent performing a CT-scan to exclude PE in 32% of our study population.