Improving lung health in low-income and middle-income countries: from challenges to solutions.

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage.

Outcomes and cost of lung cancer patients treated surgically or medically in Catalunya: cost-benefit implications for lung cancer screening programs.

Lung cancer screening programs with computed tomography of the chest reduce mortality by more than 20%. Yet, they have not been implemented widely because of logistic and cost implications. Here, we sought to: (1) use real-life data to compare the outcomes and cost of lung cancer patients with treated medically or surgically in our region and (2) from this data, estimate the cost-benefit ratio of a lung cancer screening program (CRIBAR) soon to be deployed in our region (Catalunya, Spain). We accessed the Catalan Health Surveillance System (CHSS) and analysed data of all patients with a first diagnosis of lung cancer between 1 January 2014 and 31 December 2016. Analysis was carried forward until 30 months (t = 30) after lung cancer diagnosis. Main results showed that: (1) surgically treated lung cancer patients have better survival and return earlier to regular home activities, use less healthcare related resources and cost less tax-payer money and (2) depending on incidence of lung cancer identified and treated in the program (1-2%), the return on investment for CRIBAR is expected to break even at 3-6 years, respectively, after its launch. Surgical treatment of lung cancer is cheaper and offers better outcomes. CRIBAR is estimated to be cost-effective soon after launch.

Hospitalizations due to exacerbations of COPD: A big data perspective.

BACKGROUND: Patients with Chronic Obstructive Pulmonary Disease (COPD) may suffer episodes of exacerbation (ECOPD) that require hospitalization and worsen their health status, and prognosis. We hypothesized that a detailed interrogation of health-care "big data" databases can provide valuable information to better understand the risk factors and outcomes of these episodes. MATERIAL AND METHODS: We interrogated four databases of the Catalan health-care system (>8,000,000 registries) to identify patients hospitalized because of ECOPD for the first time (index event) between 2010 and 2012. Analysis was carried forward since the index event until the end of 2014 or the death of the patient. The two years that preceded the index event were also investigated. RESULTS: We identified 17,555 patients, (≥50 years of age) hospitalized because of ECOPD (ICD9 v.9 codes at discharge) for the first time between 2010 and 2012. In this population we observed that: (1) 23% of patients die within a year after being discharged from their first ECOPD hospitalization; (2) in the remaining patients, all-cause mortality was related to the number of re-hospitalizations, particularly with early (<30 days) readmissions; (3) despite this being a 'respiratory' cohort, prescription and dispensation of drugs for cardiovascular diseases was higher than for obstructive airway diseases; and, finally, (4) lower winter ambient temperatures are associated with hospital admissions for ECOPD particularly in early re-admitters. CONCLUSIONS: Overall these results indicate under appreciation of the burden of COPD in patients hospitalized for the first time because ECOPD.

Perception of symptoms and quality of life - comparison of patients' and physicians' views in the COPD MIRROR study.

OBJECTIVES: The aim of this study was to compare potential differences between the perception that COPD patients have of their disease and the perception that physicians have of how the disease affects their patients. METHODS: Surveys in COPD patients and physicians caring for COPD patients were conducted in Spain, Italy, and Germany. Online questionnaires mirrored to explore the same domains, were administered to patients and physicians. Physicians were asked to respond to the questionnaire taking a recently seen patient who represents the majority of COPD patients usually managed, as a reference. Patients with COPD completed a survey containing the same questions offered to the physicians (Medical Investigation of Respiratory COPD Perception [MIRROR] survey). Comparisons between the responses of patients and general practitioners (GPs) and between patients and pulmonologists (PULs) were run separately using the chi-square, Fisher's exact, or Student's t-tests. RESULTS: A total of 334 COPD patients, 333 GPs, and 333 PULs participated in the surveys. The typical perception that PULs have of the COPD patient was that of an older man with more severe disease and less likely to be a smoker, than the included COPD patients. COPD was regarded as a major health problem by patients and physicians, but its impact on overall quality of life among more severe patients was less strongly perceived by physicians than by patients. Instead, physicians paid more attention to domains related to clinical features (cough, phlegm, and dyspnea), while underestimating COPD impact on leisure and social activities. The majority of patients stated not being completely frank with their doctors during visits. Both GPs and PULs seemed to recognize this issue but underestimated its extent. CONCLUSION: To improve the doctor-patient communication, a more frank reporting by the patients of their symptoms and feelings and an increased awareness of physicians about the impact on nonconventional domains that patients perceive as importantly affected by COPD should be encouraged.

Validity Study of Catalan, Galician and Basque Language Versions of the COPD Assessment Test and Equivalence With the Spanish Version. / Estudio de la validez de las versiones en catalán, gallego y vasco del cuestionario COPD assessment test y equivalencia con la versión en castellano.

OBJECTIVES: To assess the linguistic equivalence of the COPD Assessment Test versions in Catalan (CAT-C), Galician (CAT-G) and Basque (CAT-V) with the validated Spanish version (CAT) in COPD patients able to use both official languages. METHODS: Study performed in primary care centers in Catalonia, Galicia and the Basque Country. Half of the patients completed the questionnaire in their local language followed by the CAT in Spanish, while the other half did so in reverse order. RESULTS: 151 COPD patients were included in the study, with a mean age of 69.0 (SD: 9.7) years. Most (79.5%) were men, 11.3% were educated up touniversity level, and 31.8% were current smokers. Mean FEV1 was 61.4% (SD: 16.8) predicted and 83.9% of patients were GOLD grade i or ii. Concordance between CAT-C, CAT-G and CAT-V and CAT was high, with differences between scores from 0.4 to-0.5. Reliability (Cronbach's alpha) ranged from0.72 to0.86. Convergent validity, when correlated with the Medical Research Council Dyspnea scale (P=.003) and Saint George's Respiratory Questionnaire (ICC, r=0.74) scores, was significant. CONCLUSIONS: CAT-C, CAT-G and CAT-V scores were similar to CAT scores, with high correlation and concordance. These results show the equivalence between the validated Spanish CAT and the versionin other languages, so CAT-C, CAT-G and CAT-V can be used in individuals whose main language is Catalan, Galician or Basque.

Assessment of a Combined Panel of Six Serum Tumor Markers for Lung Cancer.

RATIONALE: We have previously identified six serum tumor markers (TMs) (carcinoembryonic antigen, carbohydrate antigen 15.3, squamous cell carcinoma-associated antigen, cytokeratin-19 fragment, neuron-specific enolase, and pro-gastrin-releasing peptide) related to the presence of lung cancer (LC). OBJECTIVES: To validate their individual performance in an independent cohort, and to explore if their combined assessment (≥1 abnormal TM value) is a more accurate marker for LC presence. METHODS: We determined these six TMs in 3,144 consecutive individuals referred to our institution by their primary care physician because of the clinical suspicion of LC. MEASUREMENTS AND MAIN RESULTS: LC was excluded in 1,316 individuals and confirmed in 1,828 patients (1,563 with non-small cell LC and 265 with small cell LC). This study validated the previously reported performance of each individual TM. We also showed that their combined assessment (≥1 abnormal TM) had a better sensitivity, specificity, negative predictive value, and positive predictive value (88.5, 82, 83.7, and 87.3%, respectively) than each TM considered individually and that it increased the diagnostic performance (area under the curve) of a clinical model that included tumor size, age, and smoking status. In patients with radiographic nodules less than 3 cm, the negative predictive value of the TM panel was 71.8%, hence providing some support for a more conservative diagnostic approach. Finally we identified two TMs (neuron-specific enolase and pro-gastrin-releasing peptide) that differentiate the risk of non-small cell LC from that of small cell LC. CONCLUSIONS: The combined assessment of a panel of six serum TMs is a more accurate marker for LC presence than these same TMs considered individually. The potential of these TMs in the diagnostic and screening settings deserves further research.

Assessment of health status and program performance in patients on long-term oxygen therapy.

BACKGROUND: Despite well established clinical guidelines, performance of long-term oxygen therapy (LTOT) programs shows marked variability among territories. The current study assessed the LTOT program and the health status of patients on LTOT prior to the deployment of community-based integrated care in an urban health district of Barcelona (Spain). AIMS: To assess: i) the LTOT program and health status of the patients on LTOT in the health district; ii) their frailty profile; and, iii) the requirements for effective deployment of integrated care services for these patients. METHODS: Cross-sectional observational study design including all patients (n = 406) on LTOT living in the health district. Health status, frailty, arterial blood gases, forced spirometry and hand-grip muscle strength were measured. Network analysis of frailty was carried out. RESULTS: Adequacy of LTOT prescription (n = 362): 47% and 31% of the patients had PaO2 ≤ 60 mmHg and ≤55 mmHg, respectively. Adherence to LTOT: 31% of all patients used LTOT ≥15 h/d; this figure increased to 67% in those with PaO2≤60 mmHg. Assessment of frailty: Overall, LTOT patients presented moderate to severe frailty. Care complexity was observed in 42% of the patients. CONCLUSIONS: Adequacy and adherence to LTOT was poor and many patients were frail and complex. The outcomes of the network analysis may contribute to enhance assessment of frailty in LTOT patients. These observations suggest that an integrated care strategy has the potential to improve the health outcomes of these patients.

Chronic Obstructive Pulmonary Disease heterogeneity: challenges for health risk assessment, stratification and management.

BACKGROUND AND HYPOTHESIS: Heterogeneity in clinical manifestations and disease progression in Chronic Obstructive Pulmonary Disease (COPD) lead to consequences for patient health risk assessment, stratification and management. Implicit with the classical "spill over" hypothesis is that COPD heterogeneity is driven by the pulmonary events of the disease. Alternatively, we hypothesized that COPD heterogeneities result from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering, each of them with their own dynamics. OBJECTIVE AND METHOD: To explore the potential of a systems analysis of COPD heterogeneity focused on skeletal muscle dysfunction and on co-morbidity clustering aiming at generating predictive modeling with impact on patient management. To this end, strategies combining deterministic modeling and network medicine analyses of the Biobridge dataset were used to investigate the mechanisms of skeletal muscle dysfunction. An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was performed using a large dataset (ICD9-CM data from Medicare, 13 million people). Finally, a targeted network analysis using the outcomes of the two approaches (skeletal muscle dysfunction and co-morbidity clustering) explored shared pathways between these phenomena. RESULTS: (1) Evidence of abnormal regulation of skeletal muscle bioenergetics and skeletal muscle remodeling showing a significant association with nitroso-redox disequilibrium was observed in COPD; (2) COPD patients presented higher risk for co-morbidity clustering than non-COPD patients increasing with ageing; and, (3) the on-going targeted network analyses suggests shared pathways between skeletal muscle dysfunction and co-morbidity clustering. CONCLUSIONS: The results indicate the high potential of a systems approach to address COPD heterogeneity. Significant knowledge gaps were identified that are relevant to shape strategies aiming at fostering 4P Medicine for patients with COPD.

FAQs about the GOLD 2011 assessment proposal of COPD: a comparative analysis of four different cohorts.

Since the publication of the new Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposal for the assessment of chronic obstructive lung disease (COPD), four studies have used existing cohorts to explore the characteristics, temporal variability and/or relationship with outcomes of the four resulting patient categories (A, B, C and D). Here, we compare their results and address a number of frequently asked questions (FAQs) on the topic. The most salient findings were that: 1) the prevalence of these four groups depends on the specific population studied, C being the least prevalent; 2) comorbidities are particularly prevalent in the two "high-symptom" groups (B and D); 3) patients classifiedZ as A or D tend to remain in the same group over time, whereas those classified as B or C change substantially during follow-up; 4) mortality at 3 years was lowest in A and worst in D but surprisingly similar (and intermediate) in B and C; and 5) the incidence of exacerbations during follow-up increases progressively from A to D but that of hospitalisations behave similarly to mortality. These results identify several strengths and shortcomings of the new GOLD assessment proposal, particularly that group B is associated with more morbidity and high mortality.

Expansion of the prognostic assessment of patients with chronic obstructive pulmonary disease: the updated BODE index and the ADO index.

BACKGROUND: The BODE index (including body-mass index, airflow obstruction, dyspnoea, and exercise capacity) was an important contribution to the prognostic assessment of patients with chronic obstructive pulmonary disease (COPD). However, no study has assessed whether the risk of mortality predicted by the BODE index matches the observed mortality in different populations. We assessed the calibration of the BODE index, updated it to improve its calibration, and developed and validated a simplified index for use in primary-care settings. METHODS: We included 232 patients from the Swiss Barmelweid cohort with longstanding and severe COPD and 342 patients from the Spanish Phenotype and Course of COPD cohort study who had had their first hospital admission due to moderate-to-severe COPD. In both cohorts we compared the observed 3-year risk of all-cause mortality with the risk predicted by the BODE index. We then updated the BODE index and developed a simplified ADO index (including age, dyspnoea, and airflow obstruction) from the Swiss cohort, and validated both in the Spanish cohort. FINDINGS: Calibration of the BODE index was poor, with relative underprediction of 3-year risk of mortality by 36% in the Swiss cohort (median predicted risk 21.7% [IQR 12.7-31.7] vs 34.1% observed risk; p=0.013) and relative overprediction by 39% in the Spanish cohort (16.7% [12.7-31.7] vs 12.0%; p=0.035). The 3-year risk of mortality predicted by both the updated BODE (median 10.7% [8.1-13.8]) and ADO indices (11.8% [9.1-14.3]) matched the observed mortality in the Spanish cohort well (p=0.99 and p=0.98, respectively). INTERPRETATION: Both the updated BODE and ADO indices could lend support to the prognostic assessment of patients with COPD in specialised and primary-care settings. Such assessment enhances the targeting of treatments to individual patients. FUNDING: Swiss National Science Foundation; Klinik Barmelweid; Fondo de Investigación Sanitaria Ministry of Health, Spain; Agència d'Avaluació de Tecnologia i Recerca Mèdiques, Catalonia Government; Spanish Society of Pneumology and Thoracic Surgery; Catalan Foundation of Pneumology; Red RESPIRA; Red RCESP; Fondo de Investigación Sanitaria; Fondo de Investigación Sanitaria; Fundació La Marató de TV3; Novartis Farmacèutica, Spain.