Sunday, April 23, 2017

Pauci-granulocytic stable asthma (Article from Allergy 2017)

Read new article on hot topic paucigranulocytic asthma in comparison with another inflammatory asthma phenotypes! The emergence and increasing availability of validated, feasible non-invasive methods of assessment of inflammation has led to a greater understanding of inflammatory phenotypes in asthma. Two distinct and apparently stable sputum inflammatory phenotypes have been described, eosinophilic and non-eosinophilic, which have a differential treatment response, particularly to glucocorticosteroids. The classification has been further revised:  eosinophilic, neutrophilic, mixed granulocytic (raised eosinophils and neutrophils) and paucigranulocytic (normal levels of eosinophils and neutrophils).


According to induced sputum cell count, four different asthma phenotypes have been recognised(eosinophilic, neutrophilic, mixed and pauci-granulocytic). The aim of the present study was to detect functional and inflammatory characteristics of patients with pauci-granulocytic asthma.


240 asthmatic patients were categorised in the four phenotypes according to cell counts in induced sputum. All patients underwent pulmonary function tests, and measurement of FeNO. The levels of IL-8, IL-13, and ECP were also measured in sputum supernatant. Treatment, asthma control and the presence of Severe Refractory Asthma(SRA) were also recorded.


Patients were categorized in the four phenotypes as follows: eosinophilic (40%), mixed (6.7%), neutrophilic (5.4%) and pauci-granulocytic (47.9%). Although ACT did not differ between groups (p=0.288) patients with pauci-granulocytic asthma had better lung function (FEV1%pred) (median (IQR):71.5(59.0-88.75) vs 69.0(59.0-77.6) vs 68.0(60.0-85.5) vs 80.5(69.7-95.0), p=0.009] for eosinophilic, mixed, neutrophilic and pauci-granulocytic asthma respectively, p=0.009). SRA occurred more frequently in the eosinophilic and mixed phenotype (41.6% and 43.7% respectively) and less frequently in the neutrophilic and pauci-granulocytic phenotype (25% and 21.7% respectively, p=0.01). FeNO, ECP and IL-8 were all low in the pauci-granulocytic, whereas as expected FeNO and ECP were higher in eosinophilic and mixed asthma, while IL-8 was higher in patients with neutrophilic and mixed asthma(p<0.001 for all comparisons). Interestingly, 14.8% of patients with pauci-granulocytic asthma had poor asthma control.


Pauci-granulocytic asthma most likely represents a “benign” asthma phenotype, related to a good response to treatment, rather than a “true” phenotype of asthma. However, pauci-granulocytic patients that remain not-well-controlled despite optimal treatment represent an asthmatic population that requires further study for potential novel targeted interventions.
Direct link to article:

Friday, April 14, 2017

Easter Greetings from Respiratory Decade

Dear Respiratory friends,
We want to wish Happy Easter to you and your families!
We are grateful for your outstanding contribution to Respiratory Decade in the world and your continuing support of Respiratory Decade campaign!

Friday, April 7, 2017

Phenotyping Before Starting Treatment in COPD? (Free full text from Journal of COPD 2017)

Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous and complex disease with great morbidity and mortality. Despite the new developments in the managements of COPD, it was recognized that not all patients benefit from the available medications. Therefore, efforts to identify subgroups or phenotypes had been made in order to predict who will respond to a class of drugs for COPD.
This review will discuss phenotypes, endotypes, and subgroups such as the frequent exacerbator, the one with systemic inflammation, the fast decliner, ACOS, and the one with co-morbidities and their impact on therapy. It became apparent, that the “inflammatory” phenotypes: frequent exacerbator, chronic bronchitic, and those with a number of co-morbidities need inhaled corticosteroids; in contrast, the emphysematous type with dyspnea and lung hyperinflation, the fast decliner, need dual bronchodilation (deflators). However, larger, well designed studies clustering COPD patients are needed, in order to identify the important subgroups and thus, to lead to personalize management in COPD.

This is an Accepted Manuscript of an article published by Taylor & Francis in COPD: Journal of Chronic Obstructive Pulmonary Disease on 7 April 2017, available online:

Tuesday, April 4, 2017

Triple therapy versus LAMA therapy for COPD - TRINITY study (Lancet 2017 article)


Limited data are available for the efficacy of triple therapy with two long-acting bronchodilators and an inhaled corticosteroid in chronic obstructive pulmonary disease (COPD). We compared treatment with extrafine beclometasone dipropionate, formoterol fumarate, and glycopyrronium bromide (BDP/FF/GB; fixed triple) with tiotropium, and BDP/FF plus tiotropium (open triple).


For this double-blind, parallel-group, randomised, controlled trial, eligible patients had COPD, post-bronchodilator forced expiratory volume in 1 s (FEV1) of less than 50%, at least one moderate-to-severe COPD exacerbation in the previous 12 months, and a COPD Assessment Test total score of at least 10. After a 2-week run-in period receiving one inhalation per day via single-dose dry-powder inhaler of open-label 18 μg tiotropium, patients were randomised (2:2:1) using a interactive response technology system to 52 weeks treatment with tiotropium, fixed triple, or open triple. Randomisation was stratified by country and severity of airflow limitation. The primary endpoint was moderate-to-severe COPD exacerbation rate. The key secondary endpoint was change from baseline in pre-dose FEV1 at week 52. The trial is registered with, number NCT01911364.


Between Jan 21, 2014, and March 18, 2016, 2691 patients received fixed triple (n=1078), tiotropium (n=1075), or open triple (n=538). Moderate-to-severe exacerbation rates were 0.46 (95% CI 0.41–0.51) for fixed triple, 0.57 (0.52–0.63) for tiotropium, and 0·45 (0.39–0.52) for open triple; fixed triple was superior to tiotropium (rate ratio 0.80 [95% CI 0.69–0.92]; p=0.0025). For week 52 pre-dose FEV1, fixed triple was superior to tiotropium (mean difference 0·061 L [0.037 to 0.086]; p<0·0001) and non-inferior to open triple (−0.003L [–0.033 to 0.027]; p=0.85). Adverse events were reported by 594 (55%) patients with fixed triple, 622 (58%) with tiotropium, and 309 (58%) with open triple.


In our TRINITY study, treatment with extrafine fixed triple therapy had clinical benefits compared with tiotropium in patients with symptomatic COPD, FEV1 of less than 50%, and a history of exacerbations.
Full text is

Saturday, April 1, 2017

News alert: According to the last Pharma R&D 2017 Review, Respiratory Drugs the only group decreasing

Pharma R&D 2017 Review, presented recently new drugs by Therapy Groups. Cancer at the top increasing 20%, Respiratory Drugs the only group decreasing.
It is a huge paradox, in the time when we have the progressive increasing of prevalence and mortality of chronic respiratory diseases!!!

Respiratory diseases are STILL among the leading causes of death worldwide.
Lung infections (mostly pneumonia and tuberculosis), lung cancer and chronic obstructive pulmonary disease (COPD) together accounted for 9.5 million deaths worldwide during 2008, one-sixth of the global total. The World Health Organization estimates that the same four diseases accounted for one-tenth of the disability-adjusted life-years (DALYs) lost worldwide in 2008.
The Global Burden of Disease (GBD) Study recently compared the contribution of major diseases to deaths and disability worldwide for 1990 and 2010. Among the leading causes of death, lower respiratory infections were ranked 3rd in 1990 and 4th in 2010, whereas COPD was ranked 4th in 1990 and 3rd in 2010. Lung cancer rose from 8th- to 5th- commonest cause of death, while tuberculosis fell from 6th to 10th position in the ranking.
The GBD Study also presented rankings for years lived with disability, among which asthma ranked 13th worldwide in 1990 and 14th in 2010, while COPD ranked 6th in 1990 and 5th in 2010. When premature deaths and disability were combined as DALYs  lost, lower respiratory infections were ranked the leading cause worldwide in 1990, and the 2nd most important cause of DALYs lost in 2010. Also among the 25 most important causes were COPD (ranked 6th in 1990 and 9th in 2010), tuberculosis (ranked 8th in 1990 and 13th in 2010) and lung cancer (ranked 24th in 1990 and 22nd in 2010).

Friday, March 31, 2017

Management of COPD in Patients with Cardiovascular Diseases (Hot Topic Review from Drugs 2017)

Dear Friends we are happy to present you Review from Drugs Journal on Hot Topic: Management of COPD in Patients with Cardiovascular Diseases by great Italian Respiratory team: Mario Cazzola, Luigino Calzetta, Barbara Rinaldi, Clive Page, Giuseppe Rosano, Paola Rogliani, Maria Gabriella Matera!!!
Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases often coexist. The mechanistic links between these two diseases are complex, multifactorial and not entirely understood, but they can influence the therapeutic approach. Therapy can be primarily directed towards treating the respiratory symptoms and reducing lung inflammation. Smoking cessation, bronchodilators and inhaled corticosteroids are central to this therapeutic approach.
The underlying pathophysiological mechanisms that are responsible for the increased cardiovascular risk in COPD remain unclear, but might include arterial stiffness, inflammation and endothelial dysfunction as a consequence of systemic exposure to chemicals in cigarette smoke or airborne pollution. Therefore, it is plausible that treatment of cardiovascular co-morbidities might reduce morbidity and mortality in patients with COPD and, consequently, therapy of COPD should be shifted to the treatment of cardiovascular diseases and systemic inflammation. In support of this approach, early data suggest that patients with COPD treated with angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, statins, anti-platelet drugs or β-adrenoceptor blockers may have improved survival and reduced hospitalisation from acute exacerbations of COPD. In this review, the potential impact of traditional therapies for COPD that are centred on treating the lungs and newer strategies potentially able to affect and mitigate cardiovascular risks in patients with COPD are discussed.
Full text is 

Saturday, March 25, 2017

World TB Day 2017 (special Lancet 2017 article)

Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis).
This poses several challenges similar to those encountered in the pre-chemotherapy era, including the inability to cure tuberculosis, high mortality, and the need for alternative methods to prevent disease transmission. This phenomenon mirrors the worldwide increase in antimicrobial resistance and the emergence of other MDR pathogens, such as malaria, HIV, and Gram-negative bacteria. MDR and XDR tuberculosis are associated with high morbidity and substantial mortality, are a threat to health-care workers, prohibitively expensive to treat, and are therefore a serious public health problem. In this Commission, we examine several aspects of drug-resistant tuberculosis. The traditional view that acquired resistance to antituberculous drugs is driven by poor compliance and programmatic failure is now being questioned, and several lines of evidence suggest that alternative mechanisms—including pharmacokinetic variability, induction of efflux pumps that transport the drug out of cells, and suboptimal drug penetration into tuberculosis lesions—are likely crucial to the pathogenesis of drug-resistant tuberculosis. These factors have implications for the design of new interventions, drug delivery and dosing mechanisms, and public health policy. We discuss epidemiology and transmission dynamics, including new insights into the fundamental biology of transmission, and we review the utility of newer diagnostic tools, including molecular tests and next-generation whole-genome sequencing, and their potential for clinical effectiveness. Relevant research priorities are highlighted, including optimal medical and surgical management, the role of newer and repurposed drugs (including bedaquiline, delamanid, and linezolid), pharmacokinetic and pharmacodynamic considerations, preventive strategies (such as prophylaxis in MDR and XDR contacts), palliative and patient-orientated care aspects, and medicolegal and ethical issues.

Thursday, March 23, 2017

Pneumonology Quiz – Case 5 (free article from 2017 Archives of Hellenic Medicine)

A 78-year-old male patient presented in the emergency department with a gradual deterioration of his general state of health during the preceding month. More specifically, he complained of progressive breathlessness, retrosternal pain radiating throughout his thoracic cavity, dizziness, syncopal episodes and cough, productive of small quantities of pink-tinted phlegm, mainly on exertion. At presentation, the patient appeared severely unwell. He was pale and he scored four in the modified Medical Research Council (mMRC) breathlessness score.
Pulmonary auscultation revealed bilateral coarse crackles throughout the lung fields. Heart sounds were rhythmic, characterized by a loud ejection systolic murmur clearly audible in all auscultation areas and diminished heart sounds in the aortic area. His heart rate was 80 beats per minute and his blood pressure was 100/60 mmHg.
Free full text is

Previous cases:

Pneumonology Quiz - Case 1

Pneumonology Quiz - Case 2

Pneumonology Quiz – Case 3

Pneumonology Quiz – Case 4

Tuesday, March 21, 2017

@RespiratoryBMC channel for Respiratory updates

Dear friends we are happy to present you new twitter channel @RespiratoryBMC!
@RespiratoryBMC on twitter will present OpenAccess research from the world known BioMedCentral’s Respiratory medicine journals!

The account will be covering content from all BioMedCentral’s Respiratory medicine journals Respiratory Research, Multidisciplinary Respiratory Medicine, Pneumonia, Asthma Research and Practice and COPD Research and Practice.  
FOLLOW @RespiratoryBMC!!!

Sunday, March 19, 2017

Management of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline 2017 (Free full text)

This document provides clinical recommendations for treatment of chronic obstructive pulmonary disease (COPD) exacerbations.
Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of COPD experts.
After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made: 1) a strong recommendation for noninvasive mechanical ventilation of patients with acute or acute-on-chronic respiratory failure; 2) conditional recommendations for oral corticosteroids in outpatients, oral rather than intravenous corticosteroids in hospitalised patients, antibiotic therapy, home-based management, and the initiation of pulmonary rehabilitation within 3 weeks after hospital discharge; and 3) a conditional recommendation against the initiation of pulmonary rehabilitation during hospitalisation.
The Task Force provided recommendations related to corticosteroid therapy, antibiotic therapy, noninvasive mechanical ventilation, home-based management, and early pulmonary rehabilitation in patients having a COPD exacerbation. These recommendations should be reconsidered as new evidence becomes available.
Free full text is 

Saturday, March 18, 2017

Interventions to improve inhaler technique for people with asthma (Free fulltext from 2017 The Cochrane Library)

Background to the question
Many asthma drugs are taken by an inhaler, which deposits the drug directly into the lungs. It is important that the inhaler is taken properly, so the patient gets the most benefit. Taken properly, asthma drugs can improve symptoms and reduce attacks.

Lots of people do not use their devices correctly. This means that the drug is not delivered properly to the lungs, and as a result, asthma may not be as well controlled as it should be. People also tell us that they can have more than one type of inhaler, so it is confusing to know what to do.
We wanted to find out whether teaching people with asthma how to use their inhalers works, and whether this leads to better control of symptoms and fewer attacks. It may seem obvious, but it is important that doctors and nurses know how best to help people with asthma.
Study characteristics
We found 29 studies involving 2210 people with asthma. Studies lasted between 2 and 26 weeks. Studies reported inhaler technique on a range of different checklists.
We grouped studies into three types: studies testing enhanced face-to-face training session(s), studies using multi-media to deliver inhaler training (e.g. a video, computer app or game) and studies testing devices that give people visual or audio feedback about technique.
Studies tested different types of training and used different measures to gauge success, meaning that we could not bring data together. This was particularly true when we tried to assess effects on asthma attacks, adverse events, visits to a healthcare provider and absences from work or school.
Key results
Both face-to-face and multi-media inhaler training improved inhaler technique in most studies, although results varied depending on how and when each technique was assessed.
Some studies reported the number of people who had correct or 'good enough' technique. More people had correct or 'good enough' technique after face-to-face training and with feedback devices. But the benefit of multi-media training for adults was uncertain.
Interventions that provide inhaler training may bring some benefit for quality of life and asthma control among adults and children, but results were varied and studies were small.
Children may receive some benefit but results tended to be less clear for children because fewer and smaller studies have included children as participants.
Quality of the evidence
For studies like these, it is not possible to blind people to their assigned group. This may bias how people behave or respond to questionnaires, which reduced our confidence in the findings. We were uncertain about other results because studies did not provide enough data to show clear benefit.
We cannot say for sure what is the best way to help people learn how to use their inhaler properly. It is important that patients understand how their inhaler works, so they should ask their doctor or nurse for help.
We also use Cochrane Reviews to make suggestions for future research. We suggest that trials should last longer than six months and should report adherence information. The most useful information reported was the number of people who had 'good enough' inhaler technique, so we urge future trials to report this as well.

Free full text link is 

World Sleep Day 2017

World Sleep Day is an annual event sponsored by World Sleep Society (founded by WASM and WSF) to raise awareness of sleep disorders and highlight the burden that they place on society. The next World Sleep Day will be held on Friday, March 17, 2017.

Most sleep disorders are preventable or treatable, yet less than one-third of sufferers seek professional help. Sleep problems constitute a global epidemic that threatens health and quality of life for up to 45% of the world’s population. Better understanding of sleep conditions and more research into this area of medicine will help reduce the burden of sleep disorders on society.
World Sleep Day offers a world stage to interested parties to join forces and reach their audiences. Individuals and sleep centers around the world are invited to participate to teach about the importance of sleep and the preservation of high quality, sound and sufficient sleep.

Monday, March 6, 2017

Bronchoscopic lung volume reduction procedures for COPD in 2017 (Systemic review from The Cochrane Library)


In the recent years, a variety of bronchoscopic lung volume reduction (BLVR) procedures have emerged that may provide a treatment option to participants suffering from moderate to severe chronic obstructive pulmonary disease (COPD).


To assess the effects of BLVR on the short- and long-term health outcomes in participants with moderate to severe COPD and determine the effectiveness and cost-effectiveness of each individual technique.

Search methods

Studies were identified from the Cochrane Airways Group Specialised Register (CAGR) and by handsearching of respiratory journals and meeting abstracts. All searches are current until 07 December 2016.

Selection criteria

We included randomized controlled trials (RCTs). We included studies reported as full text, those published as abstract only and unpublished data, if available.

Data collection and analysis

Two independent review authors assessed studies for inclusion and extracted data. Where possible, data from more than one study were combined in a meta-analysis using RevMan 5 software.

Main results

One RCT of 95 participants found that AeriSeal compared to control led to a significant median improvement in forced expiratory volume in one second (FEV1) (18.9%, interquartile range (IQR) -0.7% to 41.9% versus 1.3%, IQR -8.2% to 12.9%), and higher quality of life, as measured by the St Georges Respiratory Questionnaire (SGRQ) (-12 units, IQR -22 units to -5 units, versus -3 units, IQR -5 units to 1 units), P = 0.043 and P = 0.0072 respectively. Although there was no significant difference in mortality (Odds Ratio (OR) 2.90, 95% CI 0.14 to 62.15), adverse events were more common for participants treated with AeriSeal (OR 3.71, 95% CI 1.34 to 10.24). The quality of evidence found in this prematurely terminated study was rated low to moderate.
Airway bypass stents
Treatment with airway bypass stents compared to control did not lead to significant between-group changes in FEV1 (0.95%, 95% CI -0.16% to 2.06%) or SGRQ scores (-2.00 units, 95% CI -5.58 units to 1.58 units), as found by one study comprising 315 participants. There was no significant difference in mortality (OR 0.76, 95% CI 0.21 to 2.77), nor were there significant differences in adverse events (OR 1.33, 95% CI 0.65 to 2.73) between the two groups. The quality of evidence was rated moderate to high.
Endobronchial coils
Three studies comprising 461 participants showed that treatment with endobronchial coils compared to control led to a significant between-group mean difference in FEV1 (10.88%, 95% CI 5.20% to 16.55%) and SGRQ (-9.14 units, 95% CI -11.59 units to -6.70 units). There were no significant differences in mortality (OR 1.49, 95% CI 0.67 to 3.29), but adverse events were significantly more common for participants treated with coils (OR 2.14, 95% CI 1.41 to 3.23). The quality of evidence ranged from low to high.
Endobronchial valves
Five studies comprising 703 participants found that endobronchial valves versus control led to significant improvements in FEV1 (standardized mean difference (SMD) 0.48, 95% CI 0.32 to 0.64) and scores on the SGRQ (-7.29 units, 95% CI -11.12 units to -3.45 units). There were no significant differences in mortality between the two groups (OR 1.07, 95% CI 0.47 to 2.43) but adverse events were more common in the endobronchial valve group (OR 5.85, 95% CI 2.16 to 15.84). Participant selection plays an important role as absence of collateral ventilation was associated with superior clinically significant improvements in health outcomes. The quality of evidence ranged from low to high.
Intrabronchial valves
In the comparison of partial bilateral placement of intrabronchial valves to control, one trial favoured control in FEV1 (-2.11% versus 0.04%, P = 0.001) and one trial found no difference between the groups (0.9 L versus 0.87 L, P = 0.065). There were no significant differences in SGRQ scores (MD 2.64 units, 95% CI -0.28 units to 5.56 units) or mortality rates (OR 4.95, 95% CI 0.85 to 28.94), but adverse events were more frequent (OR 3.41, 95% CI 1.48 to 7.84) in participants treated with intrabronchial valves. The lack of functional benefits may be explained by the procedural strategy used, as another study (22 participants) compared unilateral versus partial bilateral placement, finding significant improvements in FEV1 and SGRQ when using the unilateral approach. The quality of evidence ranged between moderate to high.
Vapour ablation
One study of 69 participants found significant mean between-group differences in FEV1 (14.70%, 95% CI 7.98% to 21.42%) and SGRQ (-9.70 units, 95% CI -15.62 units to -3.78 units), favouring vapour ablation over control. There was no significant between-group difference in mortality (OR 2.82, 95% CI 0.13 to 61.06), but vapour ablation led to significantly more adverse events (OR 3.86, 95% CI 1.00 to 14.97). The quality of evidence ranged from low to moderate.

Authors' conclusions

Results for selected BLVR procedures indicate they can provide significant and clinically meaningful short-term (up to one year) improvements in health outcomes, but this was at the expense of increased adverse events. The currently available evidence is not sufficient to assess the effect of BLVR procedures on mortality. These findings are limited by the lack of long-term follow-up data, limited availability of cost-effectiveness data, significant heterogeneity in results, presence of skew and high CIs, and the open-label character of a number of the studies.

Free full text is HERE

Friday, March 3, 2017

The rare cause of Severe Pulmonary Hypertension (free full text from 2017 Moldovan Journal of Health Sciences)

Female patient, aged 57, retired, non-smoking, presents dyspnea on exertion, at minimal effort, chronic severe fatigue, daytime sleepiness, insomnia, broken sleep associated with snoring and apneas, nocturia (2-3 times/night), morning headaches and xerostomia, periodic pain in the periumbilical region.

From history: juvenile obesity (100 kg), hypertensive since the age of 50, presents sleep disturbances and noisy snoring for over 10 years. The physical examination reveals dry skin, mild inferior limbs edema, acrocyanosis (lips, legs), obesity with the BMI = 47 kg/m2 (m=118 kg, h=154 cm), neck girth = 43 cm, abdominal circumference = 140 cm, umbilical hernia 3x4 cm, free nasal breathing, diminished vesicular sounds, stable hemodynamics (HR= 68/min; BP= 130/80 mmHg), Mallampati score III and17 points on the Epworth Sleepiness Scale.
Chest X-ray was normal, ECG revealed signs of right ventricular strain. The EcoCG revealed slight dilation of both atria (up to 56 mm) with the left ventricle of normal dimensions and preserved ejection fraction (50%), severe right ventricle (RV) dilatation (46 mm) and severe pulmonary hypertension (pulmonary artery systolic pressure 80 mm Hg). SpO2 at rest is 95%. Spirometric and blood gazes values are as follows FEV1-81%; FVC-80%; FEV1/FVC-109%, pH 7,43; PaO2 96 mm Hg; PaCO2 44 mm Hg.
  Considering the anamnestic data and the physical examination, which are the probable causes of pulmonary hypertension?
  What tests do you suggest for confirmation? treatment is the most suitable?
  Free full text is HERE!