Controversies in COPD

Case history: A 60-year-old male presents to his general practitioner with grade 2 dyspnoea on the modified Medical Research Council (MRC) Dyspnoea Scale. In the previous week, at his yearly occupational (a large car repair workshop) check-up, his peak flow was measured and simple spirometry was performed. The occupational nurse identified potential airflow limitation. He is atopic and was a smoker up to 10 years ago, totalling a 20 pack-year smoking history. He was/is very physically active: he walks 2 km to work every work day and still plays football once a week, although he states that since last winter he has had to play in goal for the second half. He has never received any respiratory medication. What are the next steps?

Chapter summary: Our knowledge of COPD has widely expanded after decades of intensive clinical research. However, there remain many controversies surrounding when, where, by whom and for whom COPD screening and case finding with spirometry and other tools should be conducted, and often recommendations are not evidence based. Is a case like that described above worth further exploration? If it is confirmed, why was a signal of airflow limitation not picked up in previous annual check-ups (figure 1)? When does such an active worker (and sportsman) become a patient? And would you rule out asthma or ACOS? Meanwhile, COPD remains significantly underdiagnosed, with diagnosis commonly missed or delayed until the condition is advanced. It is envisaged that early diagnosis of COPD should have an impact on individual and population outcomes, but definitive confirmation proves elusive. Despite significant effort and investment, the implementation of quality spirometry is limited because of a number of hurdles and limitations, some of which are described in this chapter. The routine use of spirometry in primary care in all patients with respiratory symptoms should reduce COPD underdiagnosis.

Case history: A 75-year-old female from a rural area of Oaxaca, Mexico, reported cough and phlegm for >30 years, exertional breathlessness for 4 years and wheezing during the winter. She reported suffering from frequent respiratory infections during childhood and adolescence. The patient had cooked with wood smoke for >50 years. As a child, she helped her mother with housework, spending time in an unventilated, smoky kitchen for long periods of time. She reported no history of tobacco smoking. She is illiterate and has a very low income. The patient is overweight and presented to the COPD clinic with a moderate increase of cough, green sputum and dyspnoea. Spirometry showed an FEV₁ of 65% predicted and an FEV₁/FVC of 66. Oxygen saturation at rest was 85% and the CT showed air trapping. Is this chronic asthma, ACOS or COPD?

Chapter summary: This chapter addresses COPD causes beyond smoking, with emphasis on COPD associated with biomass (BE-COPD). Most of the information obtained from meta-analyses that focus on risk factors of COPD in nonsmokers points out that biomass is the main cause of COPD. Almost 50% of deaths from COPD in developing countries may be attributed to biomass; ∼75% of these deaths are reported in women. There are clinical differences between BE-COPD and COPD associated with tobacco smoke (TE-COPD). In contrast to smokers, these subjects mainly have the chronic bronchitis phenotype. Air trapping predominates on CT and necropsy demonstrates more severe bronchiolitis. However, lung function, exercise capacity and molecular inflammation are similar, as are comorbidities. Information relating to genetic causes, pathogenesis and treatment is scarce. Current evidence suggests that further research is needed on this topic.

Case history: A 58-year-old female presents with exertional breathlessness and spirometry shows post-bronchodilator FEV₁ of 69% predicted and FEV₁/FVC of 0.63. The bronchodilator test showed an increase in FEV₁ of 316 mL and 15%. She is a smoker of 10 cigarettes a day (18 pack-years) and reports frequent episodes of bronchitis with wheezing during childhood that were treated with parenteral corticosteroids and occasionally with antibiotics. Is this chronic asthma, COPD or another entity, and how does it alter her management?

Chapter summary: In the spectrum of chronic airway disease, some individuals share characteristics of asthma and COPD. The ACOS has been defined as symptoms of increased variability of airflow in association with non-fully reversible airflow obstruction. ∼15–20% of COPD patients may have ACOS and patients with ACOS present increased reversibility of airflow obstruction, more eosinophilic bronchial and systemic inflammation and increased response to ICSs, compared with the remaining patients with COPD. Patients with ACOS have more frequent exacerbations, more wheezing and dyspnoea and more severely impaired health status compared with COPD. From the clinician's point of view, the relevance of the ACOS is to identify patients with COPD who may have underlying eosinophilic inflammation that responds to ICSs. So far, no biomarker has been identified that allows the differentiation of ACOS from COPD, but intense investigation is being conducted to better characterise these patients at both primary and secondary healthcare levels.

Case history: A 67-year-old man is referred for assessment of dyspnoea and elevated estimated pulmonary artery systolic pressures in the 50–60 mmHg range on an echocardiogram. He has already been started on sildenafil by the referring physician for presumed pulmonary arterial hypertension. He has a 50 pack-year smoking history. His pulmonary function testing shows normal spirometry and lung volumes but a severely reduced diffusion capacity for carbon monoxide. On exam, he has crackles at the lung bases and clubbing. You order a high-resolution chest CT, which shows extensive upper lobe bullous emphysema, subpleural reticular changes and honeycombing with traction bronchiectasis at the lung bases consistent with ILD. How should this patient's lung disease be classified – as COPD, idiopathic pulmonary fibrosis, or something else? Why are his lung volumes and spirometry normal despite significant parenchymal lung disease on chest imaging? What is this patient's prognosis and how should he be managed?

Chapter summary: COPD and ILD coexist in patients not infrequently due to shared risk factors, especially tobacco smoke exposure. The coexistence of these conditions can make recognition through standard physiological studies such as spirometry and lung volume testing challenging. In such patients, recognition and diagnosis relies on measurement of lung diffusion capacity and HRCT. Coexistent COPD and ILD, frequently termed combined pulmonary fibrosis and emphysema, highlights the limitations of spirometry in the diagnosis of all COPD phenotypes as well as the central role of imaging in the assessment of patients with complex lung diseases. The natural history of coexistent COPD and ILD differs to that of either of these conditions when they occur alone. Controversies in management include the role of medications for the management of pulmonary hypertension, and the effectiveness of disease-specific medications such as bronchodilators or newer antifibrotic agents in such patients.

Case history: An 85-year-old man is seen for COPD review and his spirometry is repeated. The FEV₁ appears to have been stable over the previous 3 years. Is this compatible with COPD? How have recent data refined our knowledge on the relevance of FEV₁ decline in COPD?

Chapter summary: An accelerated decline in FEV₁ has for decades been regarded as the hallmark of COPD and most of our knowledge on risk factors for COPD comes from longitudinal studies examining a relationship between an exposure of interest and FEV₁ decline. However, FEV₁ is not a good overall measure of the processes leading to COPD and COPD progression. In particular, FEV₁ decline is not a good measure of progression of emphysema. In addition, it has been very difficult to reduce FEV₁ decline in intervention trials. As we learn more about factors in childhood affecting maximally attained lung function and different trajectories of FEV₁ leading to COPD, we get a more balanced view of the importance of FEV₁ decline.

Case history: A 62-year-old male presents with chronic exertional dyspnoea, early morning productive cough and intermittent wheezing. He is a former smoker with a smoking history of 40 pack-years. He states that his symptoms are gradually progressive, he does have “bad days of increased dyspnoea, cough and sputum” quite often, but he does not seek medical care for them as he does not want to bother his doctors. Instead, he increases his inhaled bronchodilators and reduces his activities until these episodes resolve. He has had only one medically treated exacerbation in the past year, when he had to come to the emergency room because his breathing “got really bad”. Spirometry shows severe airflow obstruction without a bronchodilator response. His outpatient medication includes a tiotropium inhaler once daily and a budesonide–formoterol inhaler twice a day. Sputum cultures carried out at this visit show 3+ Nontypeable Haemophilus influenzae (NTHi). What is the significance of his sputum culture results? How did he get colonised with NTHi, is it of clinical significance, and does it need treatment? If yes, how do we treat such colonisation?

Chapter summary: It is likely that chronic bacterial presence in COPD airways, usually referred to as colonisation, is in fact a chronic infectious state. Several investigations have now demonstrated that the presence of bacteria in the lower respiratory tract in stable COPD is associated with increased inflammation. Pathological and radiological findings in COPD support chronic infection, as do recent mouse models. Increased daily respiratory symptoms and unreported exacerbations are clinical manifestations of chronic infection in COPD. Chronic infection in this disease results from multiple impairments of innate lung immunity induced by exposure to noxious particles or gases such as tobacco smoke.

Case history: A 55-year-old obese woman presents with dyspnoea, increased production of green sputum, and low-grade fever. She has smoked for 35 years, one pack every day. A chest radiograph is equivocal for a new pulmonary infiltrate, due to her body habitus. What is the most likely diagnosis: acute pneumonia or an exacerbation of COPD?

Chapter summary: From a clinical perspective, the distinction between pneumonia and exacerbations of COPD can be challenging. Chest radiography is often required to make the distinction, but its findings may be obscured by pre-existing conditions. Biomarkers have shown the most promise: both CRP and procalcitonin can reliably distinguish between COPD exacerbations and pneumonia, but further studies are required to make final recommendations on their use. Specific and distinctive inflammatory patterns in both pneumonia with concurrent COPD and exacerbations of COPD have been typified. Although they share some similarities, the cytokine profiles and macrophage activation are different in these conditions. Inhaled steroids are used widely in COPD and are associated with an increased risk for pneumonia but not for mortality, suggesting multiple underlying mechanisms.

Case history: A 50-year-old man is seen in the clinic with newly diagnosed COPD. He is referred for smoking cessation and pulmonary rehabilitation but you feel he will also benefit from an inhaled long-acting bronchodilator. What factors would you consider in choosing the optimal medication for this man, with specific regard to the range of inhaler devices now available?

Chapter summary: Inhalation devices are a mainstay in the management of COPD. They include the pressurised metered-dose inhaler, dry powder inhaler, metered-dose inhaler with spacer, breath-actuated metered-dose inhaler, nebuliser and soft mist inhaler. Each type of device has its own advantages and disadvantages. The choice of device has to be tailored according to patient's needs, situation and preference. Certain factors, such as the age of the subject, the cognitive and psychomotor deficits occurring with the ageing process as well as a COPD-specific cognitive impairment, the availability of the drug formulation, the clinical setting as well as the disease being treated, the patient's ability to generate an adequate inspiratory flow, the capacity to handle the device appropriately and, importantly, its coordination with the inspiratory effort and the patient's preference for a device affect choice for the individual patient. Unfortunately, guidelines provide limited guidance regarding choice of devices, likely because of the lack of robust clinical data that can be translated into guideline recommendations.

Case history: Mr X is a 65-year-old patient with severe COPD (FEV₁ 35% predicted) referred to PR 2 weeks after discharge from an acute exacerbation. He has now completed 12 weeks of PR, consisting of exercise training three times per week. In addition to training, Mr X received dietary support (high protein/calorie advice), prescription of a rollator walking aid, occupational therapy (energy conservation techniques) and consultations with a respiratory nurse to develop self-management skills aiming to enhance appropriate actions upon subsequent exacerbations. Mr X improved his 6MWD by 52 m and his FEV₁ by 150 mL compared with the assessment upon entry to PR. Is this a comprehensive outcome assessment? How should the benefits of PR best be assessed?

Chapter summary: This chapter summarises the methods for assessing the effectiveness of comprehensive PR programmes, with consideration given to the different perspectives of patients, therapists, referrers and funding bodies. The assessment and treatment of PR attendees should be specific and patient centred, to maximise the attainment of individual goals across a diverse range of clinically important outcomes. The main domains of assessment include evaluation of exercise capacity, peripheral muscle strength, health-related quality of life, symptoms and physical activity levels. Assessment of additional, specific factors (e.g. nutrition, anxiety/depression, self-efficacy) may be indicated for selected patients if problems are identified upon admission to PR. Finally, consideration is given to some of the important issues affecting PR in order to improve the standardisation and comparability of future programmes.

Case history: A male patient was diagnosed with COPD by his primary care physician, who confirmed moderate airflow limitation using spirometry. His main complaint was of progressive dyspnoea. He was referred for teleconsultation by his primary care physician, which involved attendance at a local medical clinic where he was interviewed by a respiratory physician located at a large medical centre 60 miles away. His medical chart, cardiogram, spirometry and chest radiograph were forwarded to the respiratory physician. During the consultation, he was advised to stop smoking, receive regular influenza vaccinations and maintain his activity levels. The patient complained of reduced exercise tolerance and said he was becoming housebound. Although a large rehabilitation programme was operational at the main health centre 70 miles away, a small satellite six-person programme was available at a neighbouring community centre. Following referral to this programme, the patient underwent a telemedicine assessment. Once enrolled, he received online lectures in real time, simultaneously with the main rehabilitation programme. He undertook onsite exercise training supervised by a healthcare professional who was linked in real time to the physical therapist at the main centre. Following programme completion, he was followed up via teleconsultation with the nurse coordinator at the central site.

Chapter summary: Telemedicine, the provision of healthcare at a distance, is a novel approach to the management of individuals with COPD, driven by the need to facilitate access to healthcare for patients living in geographically remote regions and communities. Telemedicine applications may involve teleconsultation, telemonitoring, telehealth and telerehabilitation. Telemedicine may facilitate the early detection and management of a clinical deterioration. It aims to improve patient self-monitoring and can be used to provide patient education and rehabilitation. While patient attitudes towards this model of healthcare delivery are generally positive, the clinical benefits of telemedicine in COPD are variable and the cost-effectiveness of these interventions has not yet been determined. Despite mixed results, a select group of patients with COPD appear to benefit from differing models of telemedicine.