Changes in Control Status of COPD Over Time and Their Consequences: A Prospective International Study / Cambios en el estado de control de la EPOC a lo largo del tiempo y sus consecuencias: un estudio internacional prospectivo

INTRODUCTION: Control status may be a useful tool to assess response to treatment at each clinical visit in COPD. Control status has demonstrated to have long-term predictive value for exacerbations, but there is no information about the short-term predictive value of the lack of control and changes in control status over time. METHOD: Prospective, international, multicenter study aimed at describing the short-term (6 months) prognostic value of control status in patients with COPD. Patients with COPD were classified as controlled/uncontrolled at baseline and at 3,6-month follow-up visits using previously validated criteria of control. Moderate and severe exacerbation rates were compared between controlled and uncontrolled visits and between patients persistently controlled, uncontrolled and those changing control status over follow-up. RESULTS: A total of 267 patients were analyzed: 80 (29.8%) were persistently controlled, 43 (16%) persistently uncontrolled and 144 (53.7%) changed control status during follow-up. Persistently controlled patients were more frequently men, with lower (not increased) body mass index and higher FEV1(%). During the 6 months following an uncontrolled patient visit the odds ratio (OR) for presenting a moderate exacerbation was 3.41 (95% confidence interval (CI) 2.47-4.69) and OR = 4.25 (95%CI 2.48-7.27) for hospitalization compared with a controlled patient visit. CONCLUSIONS: Evaluation of control status at each clinical visit provides relevant prognostic information about the risk of exacerbation in the next 6 months. Lack of control is a warning signal that should prompt investigation and action in order to achieve control status

INTRODUCCIÓN: El estado de control de la enfermedad puede ser una herramienta útil para evaluar la respuesta al tratamiento de la EPOC en cada asistencia a consulta. El estado de control de la enfermedad ha demostrado tener valor predictivo a largo plazo para las exacerbaciones, pero no existe información sobre el valor predictivo a corto plazo de la falta de control de la EPOC y los cambios en dicho control a lo largo del tiempo. MÉTODO: Estudio prospectivo, internacional, multicéntrico enfocado en describir el valor pronóstico a corto plazo (6 meses) del estado de control de la enfermedad en pacientes con EPOC. Los pacientes con EPOC se clasificaron como con enfermedad controlada/sin controlar al inicio del estudio y en las 3 visitas de seguimiento separadas 6 meses, utilizando criterios de control previamente validados. Se compararon las tasas de exacerbación moderada y grave entre visitas en las que la enfermedad estaba controlada y aquellas en las que no y entre pacientes con control persistente de la enfermedad, pacientes sin control de la enfermedad y aquellos cuyo estado de control cambió durante el seguimiento. RESULTADOS: Se analizó a un total de 267 pacientes: 80 (29,8%) presentaron control persistente de la enfermedad, 43 (16%) permanecieron con enfermedad no controlada de manera persistente y 144 (53,7%) presentaron un cambio en el estado de control de su EPOC durante el seguimiento. Los pacientes con control persistente de su enfermedad fueron con mayor frecuencia hombres, con un índice de masa corporal más bajo (no elevado) y un FEV1 (%) más alto. Durante los 6 meses posteriores a una visita en la que la enfermedad del paciente no estaba controlada, la odds ratio (OR) para presentar una exacerbación moderada fue de 3,41 (intervalo de confianza [IC] del 95%: 2,47 a 4,69) y la OR = 4,25 (IC del 95%: 2,48 a 7,27) para la hospitalización, en comparación con una visita en la que la EPOC estaba controlada. CONCLUSIONES: La evaluación del estado de control de la EPOC en cada asistencia a consulta proporciona información pronóstica relevante sobre el riesgo de exacerbación en los próximos 6 meses. La falta de control es una señal de alarma que debe motivar la investigación y la acción para lograr el control de la enfermedad

Changes in Control Status of COPD Over Time and Their Consequences: A Prospective International Study.

INTRODUCTION: Control status may be a useful tool to assess response to treatment at each clinical visit in COPD. Control status has demonstrated to have long-term predictive value for exacerbations, but there is no information about the short-term predictive value of the lack of control and changes in control status over time. METHOD: Prospective, international, multicenter study aimed at describing the short-term (6 months) prognostic value of control status in patients with COPD. Patients with COPD were classified as controlled/uncontrolled at baseline and at 3,6-month follow-up visits using previously validated criteria of control. Moderate and severe exacerbation rates were compared between controlled and uncontrolled visits and between patients persistently controlled, uncontrolled and those changing control status over follow-up. RESULTS: A total of 267 patients were analyzed: 80 (29.8%) were persistently controlled, 43 (16%) persistently uncontrolled and 144 (53.7%) changed control status during follow-up. Persistently controlled patients were more frequently men, with lower (not increased) body mass index and higher FEV1(%). During the 6 months following an uncontrolled patient visit the odds ratio (OR) for presenting a moderate exacerbation was 3.41 (95% confidence interval (CI) 2.47-4.69) and OR=4.25 (95%CI 2.48-7.27) for hospitalization compared with a controlled patient visit. CONCLUSIONS: Evaluation of control status at each clinical visit provides relevant prognostic information about the risk of exacerbation in the next 6 months. Lack of control is a warning signal that should prompt investigation and action in order to achieve control status.

Predictive value of control of COPD for risk of exacerbations: An international, prospective study.

BACKGROUND AND OBJECTIVE: The concept of clinical control in COPD has been developed to help in treatment decisions, but it requires validation in prospective studies. METHODS: This international, multicentre, prospective study aimed to validate the concept of control in COPD. Patients with COPD were classified as controlled/uncontrolled by clinical criteria or CAT scores at baseline and followed up for 18 months. The main outcome was the difference in rate of a composite endpoint of moderate and severe exacerbations or death over the 18-month follow-up period. RESULTS: A total of 307 patients were analysed (mean age = 68.6 years and mean FEV1 % = 52.5%). Up to 65% and 37.9% of patients were classified as controlled by clinical criteria or CAT, respectively. Controlled patients had significantly less exacerbations during follow-up (by clinical criteria: 1.1 vs 2.6, P < 0.001; by CAT: 1.1 vs 1.9, P = 0.014). Time to first exacerbation was significantly prolonged for patients controlled by clinical criteria only (median: 93 days, IQR: 63; 242 vs 274 days, IQR: 221; 497 days; P < 0.001). Control status by clinical criteria was a better predictor of exacerbations compared to CAT criteria (AUC: 0.67 vs 0.57). CONCLUSION: Control status, defined by easy-to-obtain clinical criteria, is predictive of future exacerbation risk and time to the next exacerbation. The concept of control can be used in clinical practice at each clinical visit as a complement to the current recommendations of initial treatment proposed by guidelines.

Protocol for the EARCO Registry: a pan-European observational study in patients with α1-antitrypsin deficiency.

RATIONALE AND OBJECTIVES: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that leads to an increased risk of emphysema and liver disease. Despite extensive investigation, there remain unanswered questions concerning the natural history, pathophysiology, genetics and the prognosis of the lung disease in association with AATD. The European Alpha-1 Clinical Research Collaboration (EARCO) is designed to bring together researchers from European countries and to create a standardised database for the follow-up of patients with AATD. STUDY DESIGN AND POPULATION: The EARCO Registry is a non-interventional, multicentre, pan-European, longitudinal observational cohort study enrolling patients with AATD. Data will be collected prospectively without interference/modification of patient's management by the study team. The major inclusion criterion is diagnosed severe AATD, defined by an AAT serum level <11 µM (50 mg·dL-1) and/or a proteinase inhibitor genotype ZZ, SZ or compound heterozygotes or homozygotes of other rare deficient variants. Assessments at baseline and during the yearly follow-up visits include lung function testing (spirometry, body plethysmography and diffusing capacity of the lung), exercise capacity, blood tests and questionnaires (symptoms, quality of life and physical activity). To ensure correct data collection, there will be designated investigator staff to document the data in the case report form. All data will be reviewed by the EARCO database manager. SUMMARY: The EARCO Registry aims to understand the natural history and prognosis of AATD better with the goal to create and validate prognostic tools to support medical decision-making.

Comparison of clinical baseline characteristics between Asian and Western COPD patients in a prospective, international, multicenter study.

We aimed to compare clinical characteristics between Asian and Western chronic obstructive pulmonary disease (COPD) patients. This was a sub-analysis of an international, multicenter, prospective cohort study. Asian patients were enrolled in Singapore and South Korea. Western patients were enrolled in Spain, Poland, Ireland, the United Kingdom, and Malta. A total of 349 patients were analyzed. Among them, 110 (32%) patients were Asian and 239 (68%) Western. Male sex was more predominant in Asian than in Western (95% versus 63%, respectively; P<0.01). Body mass index was significantly lower in Asian (23.5 versus 27.1; P<0.01). The proportion of patients with a history of exacerbation was lower in Asian (12% versus 64%; P<0.01). Although patients were enrolled by same inclusion criteria, there were several differences between Asian and Western COPD patients. Our study has shown unbiased real-world differences between Asian and Western COPD patients. Since prospective follow-up study is currently ongoing, the result of this study can be fundamental base of future analysis.

Self-reported satisfaction of patients receiving omalizumab for severe allergic asthma in Malta.

Treatment satisfaction is of utmost importance for ensuring adherence. Omalizumab is administered long-term if effective and well-tolerated in a hospital setting. The aim was to evaluate treatment satisfaction with omalizumab in Malta and to identify factors that may influence patients' satisfaction. A questionnaire was distributed to all asthmatic adult patients receiving omalizumab for at least one year. The questionnaire included demographic data, dosing regimen, asthma control test and the 14-item English version of the Treatment Satisfaction Questionnaire for Medication (TSQM) Version 1.4. The TSQM 1.4 domain scores range from 0 to 100. Higher scores represent higher satisfaction. Our cohort included 33 patients (52% males), mean age 53.7 ±â€¯11 years, mean baseline IgE level 510.6IU/ml, mean duration of treatment 3.8 ±â€¯1.98 years and mean number of injections per month 4.6 ±â€¯2.6. Median TSQM scores were as follows: graded effectiveness 78%, graded side effects 100%, graded convenience 74.2% and overall satisfaction 76%. Regression analysis showed that convenience score, effectiveness score and ACT score were significantly associated with global satisfaction. Global satisfaction scored high among the Maltese cohort of patients despite the inconvenience and side effects associated with receiving omalizumab. This is an add-on beneficial effect to the efficacy and effectiveness already been achieved with this medication.

Prevalence and Characteristics of Asthma-Chronic Obstructive Pulmonary Disease Overlap in Routine Primary Care Practices.

Rationale: Adults may exhibit characteristics of both asthma and chronic obstructive pulmonary disease (COPD), a situation recently described as asthma-COPD overlap (ACO). There is a paucity of information about ACO in primary care.Objectives: To estimate the prevalence and describe characteristics of individuals with ACO in primary care practices among patients currently diagnosed with asthma, COPD, or both; and to compare the prevalence and characteristics of ACO among the three source populations.Methods: The Respiratory Effectiveness Group conducted a cross-sectional study of individuals ≥40 years old and with ≥2 outpatient primary care visits over a 2-year period in the UK Optimum Patient Care Research Database. Patients were classified into one of three source populations based on diagnostic codes: 1) COPD only, 2) both asthma and COPD, or 3) asthma only. ACO was defined as the presence of all of the following 1) age ≥40 years, 2) current or former smoking, 3) post-bronchodilator airflow limitation (forced expiratory volume in 1 second/forced vital capacity <0.7), and 4) ≥12% and ≥200 ml reversibility in post-bronchodilator forced expiratory volume in 1 second.Results: Among 2,165 individuals (1,015 COPD only, 395 with both asthma and COPD, and 755 asthma only), the overall prevalence of ACO was 20% (95% confidence interval, 18-23%). Patients with ACO had a mean age of 70 years (standard deviation, 11 yr), 60% were men, 73% were former smokers (the rest were current smokers), and 66% were overweight or obese. Comorbid conditions were common in patients with ACO, including diabetes (53%), cardiovascular disease (36%), hypertension (30%), eczema (23%), and rhinitis (21%). The prevalence of ACO was higher in patients with a diagnosis of both asthma and COPD (32%) compared with a diagnosis of COPD only (20%; P < 0.001) or asthma only (14%; P < 0.001). Demographic and clinical characteristics of ACO varied across these three source populations.Conclusions: One in five individuals with a diagnosis of COPD, asthma, or both asthma and COPD in primary care settings have ACO based on the Respiratory Effectiveness Group ACO Working group criteria. The prevalence and characteristics of patients with ACO varies across the three source populations.

Evaluation of criteria for clinical control in a prospective, international, multicenter study of patients with COPD.

BACKGROUND: The concept of clinical control in COPD has been developed to help in treatment decisions, but it requires validation in prospective studies. METHOD: This international, multicenter, prospective study aimed to validate the concept of control in COPD [control = stability (no exacerbations or impairment in CAT scores) + low impact (low level of symptoms)]. Data from the screening visit was used to: investigate the level of control, compare characteristics of patients according to the control status, and perform a sensitivity analysis of the levels of control using either clinical criteria or questionnaires (COPD Assessment Test -CAT- or Clinical COPD Questionnaire -CCQ-). RESULTS: A total of 314 patients were analysed, mean age was 68.5 years and mean FEV1 was 52.6% of predicted. According to the prespecified criteria 21% of patients were classified as controlled, all of them with mild/moderate COPD (Body mass index, Obstruction, Dyspnea and Exacerbations, -BODEx-index <5). A high level of dyspnea, a high CAT score or an exacerbation in the previous 3 months were found, using univariate analysis, to be the main reasons for patients not being classified as controlled. Multivariate analysis showed that female sex, chronic bronchitis and having exacerbations in the previous year were associated with uncontrolled COPD. Changing the severity cut off of BODEx from 5 to 3 did not change significantly the percentage of patients fulfilling the criteria of control. CONCLUSIONS: The proposed criteria of control were only fulfilled by 21% of patients. The suggested cut offs and their predictive value for poor outcomes need to be refined in prospective studies.

Extrafine Versus Fine Inhaled Corticosteroids in Relation to Asthma Control: A Systematic Review and Meta-Analysis of Observational Real-Life Studies.

BACKGROUND: The particle size of inhaled corticosteroids (ICSs) may affect airway drug deposition and effectiveness. OBJECTIVE: To compare the effectiveness of extrafine ICSs (mass median aerodynamic diameter, <2 µm) versus fine-particle ICSs administered as ICS monotherapy or ICS-long-acting ß-agonist combination therapy by conducting a meta-analysis of observational real-life asthma studies to estimate the treatment effect of extrafine ICSs. METHODS: MEDLINE and EMBASE databases were reviewed for asthma observational comparative effectiveness studies from January 2004 to June 2016. Studies were included if they reported odds and relative risk ratios and met all inclusion criteria (Respiratory Effectiveness Group/European Academy of Allergy and Clinical Immunology quality standards, comparison of extrafine ICSs with same or different ICS molecule, ≥12-month follow-up). End-point data (asthma control, exacerbations, prescribed ICS dose) were pooled. Random-effects meta-analysis modeling was used. The study protocol is published in the PROSPERO register CRD42016039137. RESULTS: Seven studies with 33,453 subjects aged 5 to 80 years met eligibility criteria for inclusion. Six studies used extrafine beclometasone propionate and 1 study used both extrafine beclometasone propionate and extrafine ciclesonide as comparators with fine-particle ICSs. The overall odds of achieving asthma control were significantly higher for extrafine ICSs compared with fine-particle ICSs (odds ratio, 1.34; 95% CI, 1.22-1.46). Overall exacerbation rate ratios (0.84; 95% CI, 0.73-0.97) and ICS dose (weighted mean difference, -170 µg; 95% CI, -222 to -118 µg) were significantly lower for extrafine ICSs compared with fine-particle ICSs. CONCLUSIONS: This meta-analysis demonstrates that extrafine ICSs have significantly higher odds of achieving asthma control with lower exacerbation rates at significantly lower prescribed doses than fine-particle ICSs.

A diagnostic dilemma in a case of pulmonary inflammatory myofibroblastic tumour.

An 18-year-old man presented to the local hospital in Malta, with dyspnoea, cough, mild haemoptysis, chest pain and night sweats. CT revealed a right hilar mass. Pleural tap, bronchoscopy and open lung biopsy were inconclusive. Biopsies obtained at repeat bronchoscopy and endobronchial ultrasound (EBUS) revealed a likely diagnosis of inflammatory myofibroblastic tumour (IMT). The patient subsequently underwent right pneumonectomy, and histology revealed the presence of two further nodules apart from the main tumour. Follow-up with positron emission tomography (PET)/CT showed the development of a right basal paracardial lesion due to recurrence and the presence of lymph node, pleural and skeletal disease. Despite radiotherapy to the recurrent nodule and chemotherapy, there was skeletal disease progression. Treatment with an anaplastic lymphoma kinase inhibitor, ceritinib, resulted in very good metabolic response. This case report highlights the importance of keeping IMT in mind when the diagnosis of lung tumours is difficult, as delayed diagnosis may lead to worsened prognosis.

Outcome of central hypoventilation secondary to childhood pertussis encephalitis in adulthood.

We present a rare case of central hypoventilation secondary to pertussis encephalopathy occurring during childhood. The patient was successfully managed by negative pressure ventilation initially until portable non-invasive ventilators became available. The patient was, unfortunately, lost to follow-up. She was reviewed in adulthood following several years of non-compliance to treatment and found asymptomatic despite chronic hypercapnoea.

The real-life clinical effects of 52 weeks of omalizumab therapy for severe persistent allergic asthma.

BACKGROUND: Omalizumab was introduced in Malta in 2011. To date, no local data have been published. OBJECTIVE: To obtain baseline characteristics of our local cohort, determine effectiveness of omalizumab at 52 weeks, compare clinical outcomes 52 weeks pre- and postomalizumab therapy and to assess its safety and tolerability. SETTING: The Mater Dei Hospital in Malta. METHOD: All consented adult patients who were eligible to start treatment with omalizumab for asthma were enrolled in this open, prospective observational real-life study. A questionnaire was completed and an Asthma Control Test and spirometry performed. Patients were reviewed on a regular basis. Any undesirable symptoms were recorded. Treatment effectiveness was evaluated at 16 and 52 weeks, during which a decision was taken whether patients were responders. Outcomes were compared 52 weeks pre- and post- treatment initiation. Main outcome measure To determine effectiveness of treatment following 1 year of omalizumab by assessing its impact on the rate of asthma-related exacerbations and health care utilization including hospitalizations. RESULTS: Our cohort included 22 patients, all non-smokers (mean age 52.7 ± 11, 64 % males). The mean baseline IgE level was 448.6 ± 444 IU/ml. At week 12, treatment was stopped in one patient due to arthralgias. The drug was stopped in two patients at week 16 due to treatment ineffectiveness. At week 20, treatment was stopped in another patient in view of arthralgias. A significant reduction in the number of asthma exacerbations (p = .03) and number of systemic steroid courses required (p = .03) was identified at 52 weeks. There was a significant improvement in the ACT score (p < .001) after 52 weeks but no significant improvement in FEV1. There was a non-significant decline in the number of hospitalizations (p = .6), asthma-related healthcare visits (p = .2) and days off work (p = .09). Adverse events occurred in 10 % of patients. Costs related to asthma hospital-stay and medicines administered during hospitalisations were decreased by half following 1 year on omalizumab. CONCLUSION: Omalizumab treatment resulted in an improved asthma control, with a significant reduction in asthma exacerbations and systemic steroid courses required and improvement on ACT score. Adverse events were infrequent and the drug was well tolerated.

Potential impact of fireworks on respiratory health.

The world-wide use of fireworks with their consequent detrimental effect on the air quality is widely recognized with elevated ambient air levels of particulate matter and its several metallic components and gases identified in several studies carried out during such events. Exposed individuals may be at risk following inhalation of such produced pollutants. This review focuses on the impact of fireworks on air quality and the potential effect of fireworks on the respiratory system of healthy individuals as well as those suffering from underlying respiratory diseases, particularly asthma and chronic obstructive pulmonary disease (COPD). This applies not only to spectators including children but also to pyrotechnicians themselves. An extensive Medline search revealed that a strong evidence of the impact of fireworks on respiratory health is lacking in susceptible as well as healthy individuals with no formal studies on COPD or asthma, other than a few case reports in the latter. The implementation of global strategies to control the use of fireworks and hence improve air quality could possibly reduce their likely detrimental effect on human respiratory health in exposed individuals, but clearly a more targeted research is needed.

A delayed diagnosis of Mounier-Kuhn syndrome.

Following a provisional diagnosis of asthma of several years' duration by his general practitioner, a 43-year-old otherwise healthy man who was a non-smoker was referred to a pulmonologist with worsening productive cough and exertional breathlessness. A thoracic CT scan revealed dilated airways (tracheal diameter 35 mm, left bronchial diameter 20 mm, right bronchial diameter 18 mm). Inflamed and easily collapsible airways were seen on bronchoscopy. The patient remained stable and was followed up with regular spirometry. A follow-up CT scan 7 years later showed tracheobronchomegaly (tracheal diameter 42 mm, left bronchial diameter 25 mm, right bronchial diameter 23 mm) with large cystic spaces consistent with Mounier-Kuhn syndrome. Repeat bronchoscopy showed a massively dilated trachea and generalised collapse on expiration with a dilated thin-walled bronchial tree. He was deemed ineligible for lung transplantation due to the extent of airway involvement making it difficult to anastomose donor lung to native tissue.

A local perspective to asthma management in the accident and emergency department in Malta.

AIM: This study was performed to assess the management of adult patients presenting to the Mater Dei Hospital Accident and Emergency (A&E) department with acute asthma. SUBJECTS AND METHODS: Asthmatic patients age 14 or older who presented to A&E department between January and October 2010 with asthma exacerbations were included. Data were collected from the clinical notes and analyzed. RESULTS: A total of 244 patients (67.2% females) were included, 126 (51.6%) were admitted, 97 (39.8%) discharged and 21 (8.6%) discharged themselves against medical advice. There was a decline in the presentations between January and July, followed by an upward trend until October (P = 0.42). Pulse oximetry was performed in 207 patients (84.8%), arterial blood gases in 133 (54.5%), peak expiratory flow rate in 106 (43.4%) and chest radiography in 206 (84.4%) patients. The respiratory rate was documented in 151 (61.8%), heart rate in 204 (83.6%) and ability to complete sentences in 123 (50.4%) patients. One hundred and ninety six patients (80.3%) were given nebulized bronchodilators, 103 (42.2%) intravenous corticosteroids, 7 (2.87%) oral corticosteroids, 109 (44.7%) oxygen, 28 (11.5%) antibiotics and 9 (3.69%) magnesium. Systemic corticosteroids and antibiotics were more commonly prescribed to patients admitted (P < 0.001). CONCLUSION: Management of acute asthma in Malta requires optimization in order to compare with international guidelines.