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2.  Reviewer acknowledgement 2014 
Contributing reviewers
The editors of Multidisciplinary Respiratory Medicine would like to thank all of our reviewers who have contributed to the journal in Volume 9 (2014).
PMCID: PMC4506463  PMID: 26191407
3.  Peripheral muscle strength and functional capacity in patients with moderate to severe asthma 
The adequate control of asthma includes the absence of nocturnal symptoms, minimal use of medication, normal or nearly normal lung function and no limitations to physical activity. The choice of a more sedentary lifestyle can lead to physical de-conditioning, thereby aggravating asthma symptoms and increasing the risk of obesity.
This study aimed at performing a battery of function-related assessments in patients with asthma and comparing them to a healthy control group.
A prospective, transversal and case–control study was designed.
It was set up at Santa Casa de Misericórdia Hospital –Sao Paulo and Nove de Julho University on a population of outpatients.
Subjects of the study were patients affected by moderate to severe asthma.
A case–control study was carried out involving 20 patients with moderate to severe asthma and 15 healthy individuals (control group). All participants underwent body composition analysis (BMI and BIA) and a controlled walk test (Shuttle test), resistance muscle test (1RM) and answered a physical activity questionnaire (IPAQ). The group with asthma also answered a questionnaire addressing the clinical control of the illness (ACQ).
In comparison to the control group (unpaired Student’s t-test), the patients with asthma had a significantly higher BMI (31.09 ± 5.98 vs. 26.68 ± 7.56 kg/m2) and percentage of body fat (38.40 ± 6.75 vs. 33.28 ± 8.23%) as well as significantly lower values regarding distance traveled on the walk test (369 ± 110 vs. 494 ± 85 meters) and metabolic equivalents (3.74 ± 0.87 vs. 4.72 ± 0.60). A strong correlation was found between the distance completed and peripheral muscle strength (r: 0.57, p < 0.05) and METs (Metabolic equivalents – minutes/week) and peripheral muscle strength of 1RM (r: 0.61, p = 0.009).
The individuals with asthma had lower functional capacity and levels of physical activity as well as a higher percentage of body fat compared to healthy individuals. This suggests that such patients have a reduced physical performance stemming from a sedentary lifestyle.
Despite the existence of few studies reporting moderate to severe asthmatic patients and functional capacity assessment, it is clear that the assessment presented in the current study is a valid and accessible tool in clinical practice.
PMCID: PMC4429482  PMID: 25973197
Asthma; Functional capacity; Obesity; Physical activity
4.  AIMAR survey on complex forms of bronchial asthma and COPD, their management and perception of critical issues 
The management of patients with complex forms of bronchial asthma and COPD is not usually addressed in the major international guidelines and management documents which exclusively address pure forms. AIMAR thus undertook a survey to obtain information about: a) the perceived frequency of complex forms of asthma/COPD in adult patients and in the elderly; b) patient management regarding the complex forms (focus on therapeutic goals and consequent treatment); c) the management problems perceived in diagnosis, management, monitoring, indices of appropriateness in pharmacological treatment and adherence to treatment.
The survey consisted of 18 multiple choice questions, completed by means of a web-based electronic form published in internet. All the data and responses inserted in the system were checked on-line for coherence and completeness directly during the phase of insertion and each participant had one only possibility of participating. The data thus collected were memorized directly within a relational database, based on consolidated open-source MySQL technology, and thus were immediately available for examination also during the course of the survey. Access to the data, mediated by a “back office” system of interrogation and report, enabled constant monitoring of the survey as it was being carried out, as well as extractions and verification, even on smaller data sets.
The survey was carried out in the full month of December 2013 and first half of January 2014. A total of 252 questionnaires were collected from the following physician groups: pneumologists (n = 180), general practitioners (GPs) (n = 32), allergologists (n = 8), internal medicine specialists (n = 20), other specialists (n = 12).
Complex forms of bronchial asthma and COPD are frequently observed and considered present in variable percentages ranging from about 10% to about 50% of patients visited and considered typical of patients with a previous history of asthma. Risk factors such as smoking, obesity, bronchial hyperreactivity and genetic predisposition are considered important. Diagnosis is difficult solely on the basis of symptoms in approximately 50% of cases, and a previous history of asthma, history of spirometry and presence of allergy are of help. Treating inflammation and reducing exacerbations are considered the key therapeutic goals and the combination of inhaled corticosteroid (ICS) and long acting β2-agonist (LABA) and monotherapy with ICS are considered the fundamental pharmacological mode for treating patients with mixed forms of bronchial asthma and COPD. Treating with only a bronchodilator is considered to be moderately risky for this type of patient. The identification and management of mixed forms result more impeded by “logistic” aspects, e.g. long waiting lists and integration with the GP, than by aspects intrinsic to the disease management itself, e.g. selecting the assessment or interpreting the outcome of the instrumental examinations. Treatment continuity and the integration between GP and specialist are the factors that most limit the management of mixed forms in the stable phase.
PMCID: PMC4232615  PMID: 25400910
Bronchial asthma; COPD; Complex forms; Online survey
5.  Obstructive sleep apnea and pulmonary function in patients with severe obesity before and after bariatric surgery: a randomized clinical trial 
The increasing prevalence of obesity in both developed and developing countries is one of the most serious public health problems and has led to a global epidemic. Obesity is one of the greatest risk factors of obstructive sleep apnea (OSA), which is found in 60 to 70% of obese patients mainly due to the buildup of fat tissue in the upper portion of the thorax and neck. The aim of the present randomized clinical trial is to assess daytime sleepiness, sleep architecture and pulmonary function in patients with severe obesity before and after bariatric surgery.
This randomized, controlled trial, was designed, conducted, and reported in accordance with the standards of The CONSORT (Consolidated Standards of Reporting Trials) Statement. Patients were divided into a bariatric surgery group and control group. The clinical evaluation was performed at the Sleep Laboratory of the Nove de JulhoUniversity (Sao Paulo, Brazil) and consisted of the collection of clinical data, weight, height, body mass index (BMI), measurements of neck and abdomen circumferences, spirometry, maximum ventilatory pressure measurements, standard overnight polysomnography (PSG) and the administration of the Berlin Questionnaire and Epworth Sleepiness Scale.
Fifty-two patients participated in the present study and performed PSG. Out of these, 16 underwent bariatric surgery. After surgery, mean BMI decreased from 48.15 ± 8.58 to 36.91 ± 6.67 Kg/m2. Significant differences were found between the preoperative and postoperative periods regarding neck (p < 0.001) and waist circumference (p < 0.001), maximum inspiratory pressure (p = 0.002 and p = 0.004) and maximum expiratory pressure (p = 0.001 and p = 0.002) for women and men, respectively, as well as sleep stage N3 (p < 0.001), REM sleep (p = 0.049) and the apnea-hypopnea index (p = 0.008).
Bariatric surgery effectively reduces neck and waist circumference, increases maximum ventilatory pressures, enhances sleep architecture and reduces respiratory sleep disorders, specifically obstructive sleep apnea, in patients with severe obesity.
Trial registration
The protocol for this study was registered with the World Health Organization (Universal Trial Number: U1111-1121-8873) and Brazilian Registry of Clinical Trials – ReBEC (RBR-9k9hhv).
PMCID: PMC4135715  PMID: 25136444
Bariatric surgery; Pulmonary function; Severe obesity; Sleep disorders; Ventilatory muscles
6.  Audit on the appropriateness of integrated COPD management: the “ALT-BPCO” project 
Non communicable chronic diseases (including respiratory ones) are the leading cause of death and disability. To cope with them we need to redesign the health system, improving primary prevention, screening, and outpatient services, while fully integrating different branches of the health service. The Italian Ministry of Health published extended guidelines on integrated COPD management (COPD-GL) in 2010. In2011 a condensed version was produced. These documents define appropriateness of management regarding both the specialist and the health service.
An internal audit on how clinical practice conforms to COPD-GL standards was implemented in one Italian region involving 29 respiratory units (RU) (65.8% of the total regional RU): data were collected from the clinical database at time zero and after 6 months. In the meantime, specialists of RU underwent education on COPD-GL.
At time zero, significant gaps between current practice and recommendations emerged both in medical practice (mean agreement 25%) and in the health organization (48%). At month 6 the gaps were reduced more in clinical practice (60.7%) than in organization (54.7%).
It is easier to resolve the gaps in specialist clinical practice than the organizational gaps, changing which is the politicians’ task. Correcting specialists’ inappropriateness may be worthless if this is not accompanied by improvement of the organizational obstacles. The search for appropriateness should not be limited only to specialists or to a strict control of drug prescription but should include all the organizational aspects. Implementation of COPD-GL calls for actions on the part of both specialists and the health system.
PMCID: PMC4122534  PMID: 25097757
Appropriateness; Assistance; Health organization; Specialized pulmonology practice
7.  Pneumocafé project: an inquiry on current COPD diagnosis and management among General Practitioners in Italy through a novel tool for professional education 
Symptoms of COPD are frequently disregarded by patients and also by general practitioners (GPs) in early stages of the disease, that consequently is diagnosed when already at an advanced grade of severity. Underdiagnosis and undertreatment of COPD and scarce use of spirometry are widely recurrent, while a better knowledge of the disease and a wider use of spirometry would be critical to diagnose more patients still neglected, do it at an earlier stage and properly treat established COPD. The aim of Pneumocafè project is to improve, through an innovative approach, the diagnosis and management of COPD at primary care level increasing the awareness of issues pertaining to early diagnosis, adequate prevention and correct treatment of the disease.
Pneumocafè is based on informal meetings between GPs of various geographical zones of Italy and their reference respiratory specialist (RS), aimed at discussing the current practice in comparison to suggestions of official guidelines, analyzing the actual problems in diagnosing and managing COPD patients and sharing the possible solution at the community level. In these meetings RSs faced many issues including patho-physiological mechanisms of bronchial obstruction, significance of clinical symptoms, patients’ phenotyping, and clinical approach to diagnosis and long-term treatment, also reinforcing the importance of a timely diagnosis, proper long term treatment and the compliance to treatment. At the end of each meeting GPs had to fill in a questionnaire arranged by the scientific board of the Project that included 18 multiple-choice questions concerning their approach to COPD management. The results of the analysis of these questionnaires are here presented.
1, 964 questionnaires were returned from 49 RSs. 1,864 questionnaires out of those received (94.91% of the total) resulted properly compiled and form the object of the present analysis. The 49 RSs, 37 males and 12 females, were distributed all over the Italian country and practiced their profession both in public and private hospitals and in territorial sanitary facilities. GPs were 1,330 males (71.35%) and 534 females (28.64%), mean age 56,29 years (range 27-70 yrs). Mean duration of general practice was 25.56 years (range: 0,5-40 yrs) with a mean of 1,302.43 patients assisted by each GP and 2,427,741 patients assisted in all. The majority of GPs affirmed that in their patients COPD has a mean-to-great prevalence and a mean/high impact on their practice, preceded only by diabetes and heart failure. Three-quarters of GPs refer to COPD guidelines and most of them believe that a screening on their assisted patients at risk would enhance early diagnosis of COPD. Tobacco smoking is the main recognized cause of COPD but the actions carried out by GPs to help a patient to give up smoking result still insufficient. The majority of GPs recognize spirometry as necessary to early COPD diagnosis, but the main obstacle pointed out to its wider use was the too long time for the spirometry to be performed. GPs’ main reason for prescribing a bronchodilator is dyspnea and bronchodilators preferably prescribed are LABA and LAMA. Control of patient’s adherence to therapy is mainly carried out by GPs checking the number of drugs annually prescribed or asking the patient during a control visit. Finally, about how many COPD patients GPs believe are in their group of assisted patients, a mean range of 25-40 patients was reported, that is consistently below the forecast based on epidemiological data and number of patients assisted by each GP.
The results obtained with this project confirm the validity of this informal approach to professional education. Furthermore, this inquiry provided important insights about the general management of COPD and the process of integration between RS and GPs activities on this disease condition in the long run.
PMCID: PMC4061438  PMID: 24944787
COPD diagnosis; Early diagnosis; General practice; GPs; Respiratory specialist; Spirometry
8.  The clinical and integrated management of COPD. An official document of AIMAR (Interdisciplinary Association for Research in Lung Disease), AIPO (Italian Association of Hospital Pulmonologists), SIMER (Italian Society of Respiratory Medicine), SIMG (Italian Society of General Medicine) 
COPD is a chronic pathological condition of the respiratory system characterized by persistent and partially reversible airflow obstruction, to which variably contribute remodeling of bronchi (chronic bronchitis), bronchioles (small airway disease) and lung parenchyma (pulmonary emphysema). COPD can cause important systemic effects and be associated with complications and comorbidities. The diagnosis of COPD is based on the presence of respiratory symptoms and/or a history of exposure to risk factors, and the demonstration of airflow obstruction by spirometry. GARD of WHO has defined COPD "a preventable and treatable disease". The integration among general practitioner, chest physician as well as other specialists, whenever required, assures the best management of the COPD person, when specific targets to be achieved are well defined in a diagnostic and therapeutic route, previously designed and shared with appropriateness. The first-line pharmacologic treatment of COPD is represented by inhaled long-acting bronchodilators. In symptomatic patients, with pre-bronchodilator FEV1 < 60% predicted and ≥ 2 exacerbations/year, ICS may be added to LABA. The use of fixed-dose, single-inhaler combination may improve the adherence to treatment. Long term oxygen therapy (LTOT) is indicated in stable patients, at rest while receiving the best possible treatment, and exhibiting a PaO2 ≤ 55 mmHg (SO2 < 88%) or PaO2 values between 56 and 59 mmHg (SO2 < 89%) associated with pulmonary arterial hypertension, cor pulmonale, or edema of the lower limbs or hematocrit > 55%. Respiratory rehabilitation is addressed to patients with chronic respiratory disease in all stages of severity who report symptoms and limitation of their daily activity. It must be integrated in an individual patient tailored treatment as it improves dyspnea, exercise performance, and quality of life. Acute exacerbation of COPD is a sudden worsening of usual symptoms in a person with COPD, over and beyond normal daily variability that requires treatment modification. The pharmacologic therapy can be applied at home and includes the administration of drugs used during the stable phase by increasing the dose or modifying the route, and adding, whenever required, drugs as antibiotics or systemic corticosteroids. In case of patients who because of COPD severity and/or of exacerbations do not respond promptly to treatment at home hospital admission should be considered. Patients with "severe" or "very severe" COPD who experience exacerbations should be carried out in respiratory unit, based on the severity of acute respiratory failure. An integrated system is required in the community in order to ensure adequate treatments also outside acute care hospital settings and rehabilitation centers. This article is being simultaneously published in Sarcoidosis Vasc Diffuse Lung Dis 2014, 31(Suppl. 1);3-21.
PMCID: PMC4107539  PMID: 25057359
COPD; Integrated care; Management
9.  AIMAR survey on COPD phenotypes 
COPD is characterized by considerable diversity in terms of clinical signs and symptoms, physiopathological mechanisms, response to treatment and disease progression. For this reason, the identification of different patient subgroups (or possible phenotypes) is important both for prognosis and for therapeutic objectives. Based on the foregoing, AIMAR has decided to conduct a survey on the perception of the prevalence of the different clinical COPD phenotypes/subtypes in the clinical practice of physicians who treat patients with chronic obstructive pulmonary disease, and on their therapeutic objectives.
The survey consisted of 19 multiple-choice questions, compiled through a form published online. All the data and answers entered into the system were checked for consistency and completeness directly online at the time they were entered, and each respondent could only complete the questionnaire once.
The survey took place from May through October 2012. A total of 1,434 questionnaires (60% of the sample approached) were eligible for analysis, broken down as follows: 537 pulmonologists, 666 general practitioners (GPs), 72 internal medicine specialists, 36 allergists, 30 geriatricians, 93 other specialists. The results show that a significant proportion of GPs (33%) identified more than 50 patients in their practices with a diagnosis of COPD. Although most patients are or have been in treatment with a long-acting bronchodilator, the most common reasons for seeing a GP or a specialist were exacerbations and worsening of the symptoms, suggesting the importance of an appropriate background therapy in order to reduce the risk of disease instability. The frequent exacerbator phenotype was the most commonly found phenotype in clinical practice (by 75% of specialists and 66% of GPs); patients with a prevalent phenotype of chronic bronchitis were reported more often by GPs, while specialists reported a higher number of patients with a prevalent phenotype of emphysema.
A medical history of exacerbations and the extent of deterioration of the spirometry parameters were considered to be the major indicators for COPD severity and clinical risk. In managing the frequent exacerbator phenotype, the therapeutic objectives – both for GPs and for specialists – included reducing airway inflammation, improving bronchial dilation, and reducing pulmonary hyperinflation. For this type of patients at high clinical risk, specialists selected a first-line therapeutic option based on a predetermined combination of an inhaled corticosteroid (ICS) and a long-acting β2-agonist bronchodilator (LABA) and a second-line three-drug therapy (combination of ICS and two long-acting bronchodilators), while GPs’ choices are more diversified, without a clear-cut prevalence of one type of treatment. In patients with COPD and concomitant cardiovascular diseases, frequently observed in clinical practice by all physicians, the combination of ICS and LABA was considered the first-choice option by the highest proportion of GPs (43%) and specialists (37%), while a smaller number of specialists (35%) opted for the long acting muscarinic antagonists (LAMA). Both GPs and specialists believe that therapeutic continuity is of primary importance for the achievement of clinical outcomes with all classes of drugs.
A good knowledge of COPD has been observed in a high percentage of GPs, indicating an increased awareness of this disease in Primary Health Care. The frequent exacerbator phenotype is viewed by all physicians as the most prevalent in clinical practice, bearing a high risk of hospitalization. For specialists, therapeutic measures aimed at reducing the number and severity of exacerbations are primarily based on the combination of inhaled corticosteroid and bronchodilator, presumably because of the complementary pharmacological action of its components, whereas while GPs’ choices tend to be more diversified. Adherence to medication regimens is of the essence for the achievement of clinical outcomes.
PMCID: PMC3994894  PMID: 24635848
COPD; Exacerbations; Online survey; Phenotypes
10.  Reviewer acknowledgement 2013 
Contributing reviewers
The editors of Multidisciplinary Respiratory Medicine would like to thank all of our reviewers who have contributed to the journal in Volume 8 (2013).
PMCID: PMC3906742  PMID: 24475757
11.  Clinical significance in COPD patients followed in a real practice 
Chronic obstructive pulmonary disease (COPD) is an important public health issue in many countries which is estimated to become the fifth cause of disability and the third cause of mortality in the world within 2020.
The objective of this study was to identify the clinical characteristics in the real clinical practice of a sample of patients with COPD followed in a pulmonology clinic.
The initial sample contained 207 subjects with respiratory claims that searched for specialized treatment and initiated regular monitoring between 2004 and 2009 in a private clinic localized in Cascavel, in the state of Parana, Brazil. Demographic data (weight, height, body mass index - BMI), history of comorbidities, use of respiratory and non respiratory drugs were also registered.
The main cause related to the development of COPD was current or prior smoking (92.0%); the most frequently reported symptom was dyspnea (95.0%), followed by cough (86.1%), wheezing (69.4%) and sputum production (40.0%). During the follow up, 51 patients developed the need for oxygen therapy (28.3%). In 96 patients, there were periods of acute exacerbation, resulting in 37 hospitalizations. In addition to COPD, a significant number of comorbidities were identified, being cardiovascular disease and neurological disorders the most prevalent ones.
Based on the data collected, we could outline the profile of patients with COPD, showing characteristics of an elderly population, with multiple comorbidities, suggesting a health related quality of life lower than expected.
PMCID: PMC3706245  PMID: 23806051
COPD; Dyspnea; Smoking
12.  Reviewer acknowledgement 2012 
Contributing reviewers
The editors of Mutlidisciplinary Respiratory Medicine would like to thank all of our reviewers who have contributed to the journal in Volume 7 (2012).
PMCID: PMC3602022  PMID: 23369543
13.  Rationale for the Turin Conference/Congress 2012 
PMCID: PMC3415118  PMID: 22958324
14.  Multistudy Fine Mapping of Chromosome 2q Identifies XRCC5 as a Chronic Obstructive Pulmonary Disease Susceptibility Gene 
Rationale: Several family-based studies have identified genetic linkage for lung function and airflow obstruction to chromosome 2q.
Objectives: We hypothesized that merging results of high-resolution single nucleotide polymorphism (SNP) mapping in four separate populations would lead to the identification of chronic obstructive pulmonary disease (COPD) susceptibility genes on chromosome 2q.
Methods: Within the chromosome 2q linkage region, 2,843 SNPs were genotyped in 806 COPD cases and 779 control subjects from Norway, and 2,484 SNPs were genotyped in 309 patients with severe COPD from the National Emphysema Treatment Trial and 330 community control subjects. Significant associations from the combined results across the two case-control studies were followed up in 1,839 individuals from 603 families from the International COPD Genetics Network (ICGN) and in 949 individuals from 127 families in the Boston Early-Onset COPD Study.
Measurements and Main Results: Merging the results of the two case-control analyses, 14 of the 790 overlapping SNPs had a combined P < 0.01. Two of these 14 SNPs were consistently associated with COPD in the ICGN families. The association with one SNP, located in the gene XRCC5, was replicated in the Boston Early-Onset COPD Study, with a combined P = 2.51 × 10−5 across the four studies, which remains significant when adjusted for multiple testing (P = 0.02). Genotype imputation confirmed the association with SNPs in XRCC5.
Conclusions: By combining data from COPD genetic association studies conducted in four independent patient samples, we have identified XRCC5, an ATP-dependent DNA helicase, as a potential COPD susceptibility gene.
PMCID: PMC2937234  PMID: 20463177
emphysema; genetic linkage; metaanalysis; single nucleotide polymorphism
16.  Outpatient vs. home-based pulmonary rehabilitation in COPD: a randomized controlled trial 
Chronic obstructive pulmonary disease (COPD) is a common cause of morbidity and mortality affecting a large number of individuals in both developed and developing countries and it represents a significant financial burden for patients, families and society. Pulmonary rehabilitation (PR) is a multidisciplinary program that integrates components of exercise training, education, nutritional support, psychological support and self-care, resulting in an improvement in dyspnea, fatigue and quality of life. Despite its proven effectiveness and the strong scientific recommendations for its routine use in the care of COPD, PR is generally underutilized and strategies for increasing access to PR are needed. Home-based self-monitored pulmonary rehabilitation is an alternative to outpatient rehabilitation. In the present study, patients with mild, moderate and severe COPD submitted to either an outpatient or at-home PR program for 12 weeks were analyzed.
Patients who fulfilled the inclusion criteria were randomized into three distinct groups: an outpatient group who performed all activities at the clinic, a home-based group who performed the activities at home and a control group. PR consisted of a combination of aerobic exercises and strengthening of upper and lower limbs 3 times a week for 12 weeks.
There was a significant difference in the distance covered on the six-minute walk test (p < 0.05) and BODE index (p < 0.001) in the outpatient and at-home groups after participating in the rehabilitation program compared to baseline.
A home-based self-monitoring pulmonary rehabilitation program is as effective as outpatient pulmonary rehabilitation and is a valid alternative for the management of patients with COPD.
PMCID: PMC3463054  PMID: 22958267
COPD; home-based pulmonary rehabilitation; pulmonary rehabilitation

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