bluuebunny/crossref_metadata_2025 huggingface dataset:
The assessment of new drugs for asthma and COPD: a Delphi study examining the perspectives of Italian payers and clinicians
Authors: Sommariva Silvia , Finch Aureliano P. , Jommi Claudio
Published: January 2020

Background: Asthma and chronic obstructive pulmonary disease (COPD) are disorders of the lungs characterized by airflow obstruction, inflammation and tissue remodeling. Management of patients with these diseases is complex and the improvement of diagnostic-therapeutic strategies represents a critical challenge for the healthcare system. In this context, investigating the criteria and information needed for an appropriate and effective evaluation of incoming treatment options is crucial to ensure that clinicians and policy-makers are provided with the best available evidence to make decisions aimed at improving patient outcomes. Therefore, the objective of this study was to investigate the degree of agreement among Health Technology Assessment (HTA) experts on issues crucial to the evaluation of new drugs for asthma and COPD and to appropriately manage the clinical pathway for patients.

Methods: This research was conducted using an e-Delphi technique organized in three subsequent rounds and involving a panel of ten experts (six regional and local payers and four clinicians). Panelists were asked to comment in written form on a set of statements, explaining qualitatively the extent to which they agreed or disagreed with the assertions. Statements were subsequently modified and resubmitted for assessment.

Results: Panelists expressed their opinions during each round and, after round III, a consensus document was finalized. The degree of consensus was high among experts and concerned five main topics: (a) the need to address current unmet needs of patients with asthma or COPD, (b) the importance of further studies and real-life information in the evaluation of treatments, (c) existing evidence and evidence needed to assess drugs, (d) critical issues in obtaining a positive evaluation from regional and local authorities for new treatments to be included in regional formularies and to have an important place in therapeutic categories, and (e) the major obstacles to the appropriate administration of drugs and management of patients.

Conclusion: The final document highlights that no proof of difference among drugs exists, that evidence on final endpoints (and particularly on mortality) should be strengthened and that actions regarding risk factors, appropriate diagnosis, patient staging and adherence to therapy are particularly important for a better clinical management.
N-acetylcysteine in COPD: why, how, and when?
Authors: Sanguinetti Claudio M.
Published: January 2020

Oxidants have long been recognized to have an important role in the pathogenesis of COPD, and in this cigarette smoke has a strong responsibility, because it generates a conspicuous amount of oxidant radicals able to modify the structure of the respiratory tract and to enhance several mechanisms that sustain lung inflammation in COPD. In fact, oxidative stress is highly increased in COPD and natural antioxidant capacities, mainly afforded by reduced glutathione, are often overcome. Thus an exogenous supplementation of antioxidant compounds is mandatory to at least partially counteract the oxidative stress. For this purpose N-acetylcysteine has great potentialities due to its capacity of directly contrasting oxidants with its free thiols, and to the possibility it has of acting as donor of cysteine precursors aimed at glutathione restoration. Many studies in vitro and in vivo have already demonstrated the antioxidant capacity of NAC. Many clinical studies have long been performed to explore the efficacy of NAC in COPD with altern results, especially when the drug was used at very low dosage and/or for a short period of time. More recently, several trials have been conducted to verify the appropriateness of using high-dose NAC in COPD, above all to decrease the exacerbations rate. The results have been encouraging, even if some of the data come from the most widely sized trials that have been conducted in Chinese populations. Although other evidence should be necessary to confirm the results in other populations of patients, high-dose oral NAC nevertheless offers interesting perspectives as add-on therapy for COPD patients.
Particulate matters from diesel heavy duty trucks exhaust versus cigarettes emissions: a new educational antismoking instrument
Authors: De Marco Cinzia , Ruprecht Ario Alberto , Pozzi Paolo , Munarini Elena , Ogliari Anna Chiara , Mazza Roberto , Boffi Roberto
Published: January 2020

Background: Indoor smoking in public places and workplaces is forbidden in Italy since 2003, but some health concerns are arising from outdoor secondhand smoke (SHS) exposure for non-smokers. One of the biggest Italian Steel Manufacturer, with several factories in Italy and abroad, the Marcegaglia Group, recently introduced the outdoor smoking ban within the perimeter of all their factories. In order to encourage their smoker employees to quit, the Marcegaglia management decided to set up an educational framework by measuring the PM1, PM2.5 and PM10 emissions from heavy duty trucks and to compare them with the emissions of cigarettes in an indoor controlled environment under the same conditions.

Methods: The exhaust pipe of two trucks powered by a diesel engine of about 13.000/14.000 cc3 were connected with a flexible hose to a hole in the window of a container of 36 m3 volume used as field office. The trucks operated idling for 8 min and then, after adequate office ventilation, a smoker smoked a cigarette. Particulate matter emission was thereafter analyzed.

Results: Cigarette pollution was much higher than the heavy duty truck one. Mean of the two tests was: PM1 truck 125.0(47.0), cigarettes 231.7(90.9) p = 0.002; PM2.5 truck 250.8(98.7), cigarettes 591.8(306.1) p = 0.006; PM10 truck 255.8(52.4), cigarettes 624.0(321.6) p = 0.002.

Conclusions: Our findings may be important for policies that aim reducing outdoor SHS exposure. They may also help smokers to quit tobacco dependence by giving them an educational perspective that rebuts the common alibi that traffic pollution is more dangerous than cigarettes pollution.
Does homeopathic medicine have a preventive effect on respiratory tract infections? A real life observational study
Authors: Beghi Gianfranco Maria , Morselli-Labate Antonio Maria
Published: January 2020

Background: Homeopathic medicine is a branch of integrative medicine that has been gaining increasing popularity. However, its clinical application remains controversial. To improve the understanding of homeopathy, observational studies-which monitor the effects of homeopathy in real-life clinical settings-are a helpful adjunct to randomized controlled trials. The goal of this controlled observational study was to investigate the role of the homeopathic medicine in preventing respiratory tract infections (RTIs). Methods: This retrospective analysis of patients’ medical records focused on a single centre from 2002 to 2011, and examined 459 patients, out of whom 248 were treated with homeopathic medicine (specific extract of duck liver and heart) and 211 were not treated. All patients were followed-up for at least 1 year, and up to a maximum of 10 years. Results: A significant reduction in the frequency of onset of RTIs was found in both the homeopathic medicine and untreated groups. The reduction in the mean number of RTI episodes during the period of observation vs. the year before inclusion in the study was significantly greater in the homeopathic-treated group than in untreated patients (-4.76 ± 1.45 vs. -3.36 ± 1.30; p = 0.001). The beneficial effect of the homeopathic medicine was not significantly related to gender, age, smoking habits or concomitant respiratory diseases when compared to the effect observed in untreated patients. Conclusion: These results suggest that homeopathic medicine may have a positive effect in preventing RTIs. However, randomized studies are needed before any firm conclusion can be reached.
Tracheobronchopathia osteochondroplastica: a rare case report of a non-smoker and non-atopic patient, with a long history of wheezing since childhood
Authors: Pirina Pietro , Fois Alessandro G. , Arcadu Antonella , Santoru Luigi , Trisolini Rocco , Marras Vincenzo , Ginesu Giorgio C. , Canu Sara , Cordero Lorenzo , Diana Gabriella
Published: January 2020

Background: Tracheobronchopathia osteochondroplastica (TBPO) is an uncommon and benign condition characterized by osseous or metaplastic cartilaginous 1–3 mm nodules in the submucosa of the tracheobronchial tree. Posterior membranous wall of trachea is typically spared. Ecchondrosis and exostosis nodules can cause chronic inflammation and mucosal metaplasia, stiffness and airway obstruction. The prevalence of this disease, often asymptomatic or associated with nonspecific symptoms, is underestimated, and the mean age at diagnosis is 50 years. Case presentation: We report a case of a 49-year old male, non-smoker. He was a smith, homeless, born in Romania and reported a diagnosis of asthma since childhood. He was admitted to our Respiratory Unit presenting low-grade fever with profuse sweating, cough, purulent sputum, and ground-glass opacity with irregularity in main bronchi detected by High-Resolution Computed Tomography (HRCT) scan. Fibrobronchoscopy revealed the presence of mucosal irregularities up to the segmental bronchi entrance. Histological examination showed nodules of osseouscartilaginous nature, consistent with TBPO. Microbiological tests of Bronchoalveolar Lavage fluid also revealed an infection by Pseudomonas Aeruginosa. Conclusion: TBPO is a rare disease characterized by wheezing, cough, hemoptysis, and recurrent pulmonary infections, with typical onset during adulthood. In the case reported, the symptoms began in childhood, although they had been misinterpreted as asthma. Even if childhood-onset is not reported in literature, it is likely that small changes occur in the first few years of life and become more evident in adulthood. The involvement of segmental and sub-segmental bronchi, usually spared in TBPO, could explain the presence of wheezing and non-productive cough reported by our patient since childhood.
Placement of self-expandable bifurcated metallic stents without use of fluoroscopic and guidewire guidance to palliate central airway lesions
Authors: Özdemir Cengiz , Sökücü Sinem Nedime , Karasulu Levent , Tural Önür Seda , Dalar Levent
Published: January 2020

Background: Self-expandable metallic stents (SEMS) can be used to treat malignant obstructions and fistulas of the central airways. SEMS can be placed using different methods. Recently, a rigid bronchoscope has been used for stent placement without the need for fluoroscopy. We retrospectively evaluated patients for whom SEMS were placed using a rigid bronchoscope, without employing guidewires or fluoroscopy. We describe the intra- and post-procedural complications of the method. Methods: Data collected between January 2014 and July 2015 were retrospectively evaluated by reference to hospital records. Results: The mean patient age was 58.14 ± 8.48 years (44–72 years) and 13 out of the 14 patients were male. Twelve had lung cancer, one a thyroid papillary carcinoma with a bronchomediastinal fistula, and one an esophageal carcinoma with a tracheoesophageal fistula. Covered metallic Y-shaped stents were placed in all patients. Before placement, argon plasma coagulation was performed on two patients, diode laser treatment on four, and de-obstruction on nine. No procedure-related mortality was noted. Only two patients required follow-up in the intensive care unit; they were moved to a regular ward after two days. No patient required stent replacement or repositioning. The most common early complication was mucus plugs. Conclusion: Endobronchial placement of covered self-expandable metallic stents was safe and readily performed in patients with airway obstructions. Neither fluoroscopic nor guidewire guidance was required. Neither patients nor staff were exposed to radiation, and costly guidewire guidance was not necessary. The procedure is cost-effective.
Effectiveness, safety and tolerability of a complex homeopathic medicinal product in the prevention of recurrent acute upper respiratory tract infections in children: a multicenter, open, comparative, randomized, controlled clinical trial
Authors: Jong Miek C. , Buskin Stephen L. , Ilyenko Lydia , Kholodova Irina , Burkart Julia , Weber Stephan , Keller Thomas , Klement Petra
Published: January 2020

Background: The present study was initiated to investigate the effectiveness, safety and tolerability of complex homeopathic CalSuli-4-02 tablets on prevention of recurrent acute upper respiratory tract infections (URTIs) in children, in comparison to another complex homeopathic product. Methods: The study was designed as a prospective, multicenter, randomized, open, clinical trial with two parallel treatment groups at four outpatient pediatric clinics in Russia. Children aged ≤ 6 years with susceptibility to acute URTIs (≥ three occasions during the last 6 months) were randomized to receive either CalSuli-4-02 or a comparator homeopathic product (control group) for 3 weeks. Primary outcome was the frequency of acute URTIs after 3 and 6 months post-treatment follow-up. Secondary endpoints were changes in complaints and symptoms (total and individual scores), treatment satisfaction, antibiotic use, safety and tolerability. Results: The intention-to-treat analysis involved 200 children (CalSuli-4-02: N = 99, Control: N = 101). In both treatment groups, the median number of acute URTIs was one for 3 months and two, respectively, for the full 6 months post-treatment (Relative Risk: 0.86 (95 %-CI: 0.72–1.03), p = 0.1099). Seasons had no influence on the outcome. At the end of study, CalSuli-4-02 had overall higher odds of getting lower complaints severity total score (Odds ratio: 1.99 (95 %-CI: 1.31–3.02), p = 0.0012) and showing symptom improvement (Odds ratio: 1.93 (95 %-CI: 1.25–3.00), p = 0.0033). Specifically, the complaint “appetite disorder” and the symptom “child’s activities” significantly improved more in the CalSuli-4-02 group (p = 0.0135 and p = 0.0063, respectively). Antibiotic use was decreased in both treatment groups at the study end. Overall assessment for satisfaction with and tolerability of treatment was higher with CalSuli-4-02. A low number of non-serious adverse drug reactions was reported (CalSuli-4-02: N = 4, Control: N = 1). Conclusions: Both complex homeopathic products led to a comparable reduction of URTIs. In the CalSuli-4-02 group, significantly less URTI-related complaints and symptoms and higher treatment satisfaction and tolerability were detected. The observation that the use of antibiotics was reduced upon treatment with the complex homeopathic medications, without the occurrence of complications, is interesting and warrants further investigations on the potential of CalSuli-4-02 as an antibiotic sparing option. Clinical trial registration number: Roszdravnadzor: Study No 164–563
Evaluation of the rapid immunochromatographic ODK0501 assay for Streptococcus pneumoniae antigen detection with nasopharyngeal swabs: preliminary report
Authors: Nishimura Naoki , Suzuki Shoji , Jinta Torahiko , Yamano Yasuhiko , Ishikawa Genta , Tomishima Yutaka , Uchiyama Noboru , Chohnabayashi Naohiko
Published: January 2020

Background: Early identification and control of pathogenic bacteria are important in the treatment of pneumonia. Currently, two rapid antigen detection kits for pneumococcal pneumonia are available: one uses urine samples and the other, named RAPIRUN® S. pneumoniae, uses sputum samples. RAPIRUN® has shown high sensitivity with nasopharyngeal swab samples from pediatric patients. In this study, we investigated the performance of RAPIRUN® with nasopharyngeal swabs from adult patients. Methods: All adult patients diagnosed with pneumonia from November 2011 to April 2012 in St. Luke’s International hospital were included in this cross-sectional study. Single sputum, nasopharyngeal swab, and urine samples obtained from patients were investigated using a rapid antigen detection kit. Sputum and blood cultures were also evaluated. We compared the characteristics of pneumococcal pneumonia patients diagnosed using RAPIRUN with a nasopharyngeal swab to those patients diagnosed using other methods. Sensitivity and specificity were also calculated. Results: Seventeen out of 60 patients with pneumonia were diagnosed with pneumococcal pneumonia. In 4 out of the 17 cases, a positive test result was obtained using RAPIRUN with a nasopharyngeal swab. The sensitivity and specificity were 23.5 and 100 %, respectively. Conclusion: RAPIRUN performed with nasopharyngeal swabs from adult patients exhibited lower sensitivity for the diagnosis of pneumococcal pneumonia than the other compared methods. The causative pathogen of pneumonia should be identified using not only sputum cultures or rapid antigen detection kits but also clinical features or gram staining of sputum.
Most Italians attending a congress on health of elderly people do not know and do not recognize respiratory diseases
Authors: Ciancio Nicola , Sanguinetti Claudio M. , Falcone Franco , Taranto Claudio , Fasani Roberto , De Benedetto Fernando , Resta Onofrio , De Michele Fausto , Messina Roberto , Rossi Andrea , Nardini Stefano , Di Maria Giuseppe
Published: January 2020

Background: The present study reports the results of a survey jointly carried out by three Italian respiratory scientific associations (AIMAR, AIPO, SIMeR) together with an important Federation of elderly patients (FederAnziani) during the National Conference of Italian Court for Health Right held in Rimini from November 29th to December 1st, 2013. The survey, based on a spirometric examination preceded by a questionnaire on respiratory health, was conducted on elderly people coming from all Italian regions to attend the Conference. Methods: Nine hundred forty-nine subjects (574 females and 375 males), mean age 66.2 ± 10.1 years, were interviewed and performed spirometric examination. There were 137 smokers (14.4 %). Mean value of Body Mass Index (BMI) was significantly higher in males (27.6 ± 6.6) than in females (26.3 ± 4.3). Results: 17.1 % (N = 143) of the studied subjects reported to be suffering from respiratory disease and the prevalent illnesses were asthma (31.5 %) and COPD/emphysema (24.5 %), but only 3.3 % of the whole surveyed group was able to identify COPD as a pulmonary disease, however without knowing its characteristics, while these were known by 0.5 % of the interviewed subjects only. A high number of subjects, 22 % of whom were smokers, declared chronic sputum production. 10.2 % of the study group showed an obstructive defect at spirometry when the criterium of lower limit of the normal (LLN) was considered, whereas it was 12.4 % if the fixed limit of 0.70 was chosen. 64 % of the obstructed people thought they did not have any respiratory disease. Conclusions: The results of this survey, able to spread the knowledge of respiratory diseases and spirometry in a wide sample of subjects for the most part scarcely aware of them, emphasize the need for a greater divulgation of respiratory issues among the general population.
Cultural and linguistic validation of the NHQ-2 Questionnaire: a specific instrument for assessing patient’s usability of inhalation devices
Authors: Dal Negro Roberto W. , Povero Massimiliano
Published: January 2020

Background: An increasing number of inhalation devices are presently available in the market. They are differently characterized in terms of their handling and usability, both factors which may affect the outcomes of respiratory treatment. The assessment of the preference and the usability rate of all devices can be carried out by means of specific questionnaires. Before their use, the identification of errors due to the incorrect wording of questions included in the questionnaires, together with the trans-cultural reliability represents the main issues of their cultural and linguistic validation. Methods and results: The New Handling Questionnaire - NHQ-2 is a novel specific questionnaire aimed to measure both the preference and the usability of all kinds of inhalation devices. The method used for its validation has been summarized in the first section of the present paper, while the results of the specific validation and translation process have been described in the second section, together with the grading of improvement achieved over the process. The comprehensibility and the reproducibility rates achieved for both the Italian and the English final versions of the NHQ-2 questionnaire were very high, such as >90 % for each question included. Conclusions: The novel NHQ-2 questionnaire proved very high comprehensibility and reproducibility in both its Italian and English final versions. It can be proposed for the trans-cultural clinical use when the usability, and not only the patients’ preference of devices, should be assessed.
Preliminary study on the assessment of visceral adipose tissue using dual-energy xray absorptiometry in chronic obstructive pulmonary disease
Authors: De Blasio Francesca , Rutten Erica P.A. , Wouters Emiel F.M. , Scalfi Luca , De Blasio Francesco , Akkermans Marco A. , Spruit Martijn A. , Franssen Frits M.E.
Published: January 2020

Background: Visceral adipose tissue (VAT) was shown to be increased in patients with chronic obstructive pulmonary disease (COPD) compared to control subjects with comparable body mass index (BMI). Our aim was to determine the relation of VAT by dual-energy x-ray absorptiometry (DEXA) in patients with COPD by disease severity, BMI, other indices of body composition and static lung volumes. Methods: 294 COPD patients admitted for rehabilitation were studied. Lung function, static lung volumes and body composition (i.e. BMI, waist circumference, fat-free mass, fat mass and fat distribution between android and gynoid fat mass) were assessed before entering pulmonary rehabilitation. VAT was estimated within the android region by using DEXA. Patients were stratified for gender, BMI (cut-off of 25 kg/m2) and GOLD stage. To assess the impact of VAT on lung volumes, patients were also stratified for VAT less and above 50th percentile. Results: Both male and female patients with more severe airflow limitation had significantly lower VAT values, but these differences disappeared after stratification for BMI. VAT was significantly and strongly correlated with other body composition parameters (all p < 0.001). Patients with moderate to severe airflow limitation and lower VAT had increased static lung hyperinflation and lower diffusing capacity for carbon monoxide. Nevertheless, multivariate stepwise regression models including for BMI, age, gender and forced expiratory volume in 1 s (FEV1) as confounders did not confirm an independent role for VAT on static lung hyperinflation and diffusion capacity. Conclusion: After stratification for BMI, VAT is comparable in moderate to very severe COPD patients. Furthermore, BMI and demographics, but not VAT, were independent predictors of static lung hyperinflation and diffusing capacity in COPD.
Pulmonary arterial hypertension associated with interferon therapy: a population-based study
Authors: Papani Ravikanth , Duarte Alexander G. , Lin Yu-li , Kuo Yong-Fang , Sharma Gulshan
Published: January 2020

Background: Isolated cases of pulmonary arterial hypertension (PAH) with interferon α or β therapy have been reported, but no population-based estimates of the incidence of the disease after interferon exposure are available. The aim of this study was to determine the incidence of PAH after initiation of interferon therapy, using a large commercial insurance database.
Methods: Using National Drug Codes (NDCs) and Healthcare Common Procedure Coding System (HCPCS) codes, we utilized the Clinformatics™ Data Mart (CDM) database to identify subjects between 20 and 65 years old who received α or β interferon therapy between April 2001 and December 2012. Patients were followed from one year prior to the first medication claim for interferon to the first diagnosis of pulmonary hypertension using ICD-9-CM codes 416.0 and 416.8, or disenrollment. In those subjects diagnosed with pulmonary hypertension, a prescription for PAH-specific medications was used as a surrogate endpoint.
Results: We identified 20,113 subjects who received interferon therapy during the study period. The median follow-up was 20 months. Pulmonary hypertension occurred in 71 subjects, and PAH-specific medications were prescribed to 7 of these subjects.
Conclusion: Although our analysis showed that the development of PAH is a rare event with
Longitudinal assessment of bleomycin-induced lung fibrosis by Micro-CT correlates with histological evaluation in mice
Authors: Stellari Franco Fabio , Ruscitti Francesca , Ravanetti Francesca , Essers Jeroen , Ridwan Yanto , Belenkov Sasha , Vos Wim , Ferreira Francisca , KleinJan Alex , Van Heijningen Paula , Van Holsbeke Cedric , Cacchioli Antonio , Villetti Gino
Published: January 2020

Background: The intratracheal instillation of bleomycin in mice induces early damage to alveolar epithelial cells and development of inflammation followed by fibrotic tissue changes and represents the most widely used model of pulmonary fibrosis to investigate human IPF. Histopathology is the gold standard for assessing lung fibrosis in rodents, however it precludes repeated and longitudinal measurements of disease progression and does not provide information on spatial and temporal distribution of tissue damage. Here we investigated the use of the Micro-CT technique to allow the evaluation of disease onset and progression at different time-points in the mouse bleomycin model of lung fibrosis. Micro-CT was throughout coupled with histological analysis for the validation of the imaging results.

Methods: In bleomycin-instilled and control mice, airways and lung morphology changes were assessed and reconstructed at baseline, 7, 14 and 21 days post-treatment based on Micro-CT images. Ashcroft score, percentage of collagen content and percentage of alveolar air area were detected on lung slides processed by histology and subsequently compared with Micro-CT parameters.

Results: Extent (%) of fibrosis measured by Micro-CT correlated with Ashcroft score, the percentage of collagen content and the percentage of alveolar air area (r2 = 0.91; 0.77; 0.94, respectively). Distal airway radius also correlated with the Ashcroft score, the collagen content and alveolar air area percentage (r2 = 0.89; 0.78; 0.98, respectively).

Conclusions: Micro-CT data were in good agreement with histological read-outs as micro-CT was able to quantify effectively and non-invasively disease progression longitudinally and to reduce the variability and number of animals used to assess the damage. This suggests that this technique is a powerful tool for understanding experimental pulmonary fibrosis and that its use could translate into a more efficient drug discovery process, also helping to fill the gap between preclinical setting and clinical practice.
Erratum to: The evidence on tiotropium bromide in asthma: from the rationale to the bedside
Authors: Radovanovic Dejan , Santus Pierachille , Blasi Francesco , Mantero Marco
Published: January 2020

After publication of the Review article it was brought to our attention that the sentence at the bottom of the

section entitled Tiotropium bromide must be corrected as follows:

“Following positive large efficacy and safety trials in asthma, in 2014 the European Medicines Agency has extended the indication of tiotropium Respimat®....
Antibiotic therapy, supportive treatment and management of immunomodulation inflammation response in community acquired pneumonia: review of recommendations
Authors: Mantero Marco , Tarsia Paolo , Gramegna Andrea , Henchi Sonia , Vanoni Nicolò , Di Pasquale Marta
Published: January 2020

Community-acquired pneumonia is a common and serious disease, with high rates of morbidity and mortality. Management and treatment of community-acquired pneumonia are described in three main documents: the 2007 American Thoracic Society guidelines, the 2011 European Respiratory Society guidelines, and the 2009 British Thoracic Society guidelines, updated by the NICE in 2015. Despite the validity of current guidelines in improving prognosis and management of patients with community-acquired pneumonia, not all recommendations have high levels of evidence and there are still some controversial issues. In particular, there are some areas of low evidence such as the efficacy of an antibiotic molecule or scheme in patients with same risk factors; duration of antibiotic treatment, supportive therapy for acute respiratory failure and immunomodulation molecules. This review will summarize the main recommendations with high level of evidence and discuss the recommendations with lower evidence, analyzing the studies published after the guidelines’ release.
Non-typeable Haemophilus Influenzae detection in the lower airways of patients with lung cancer and chronic obstructive pulmonary disease
Authors: Sriram Krishna B.
Published: January 2020

Background: Chronic airway inflammation and hypersensitivity to bacterial infection may contribute to lung cancer pathogenesis. Previous studies have demonstrated that nontypeable Haemophilus influenzae (NTHi) is the most common colonizing bacteria in the lower airways of patients with COPD. The objective of this study was to determine the presence of NTHi and immunoglobulin concentrations in patients with lung cancer, COPD and controls. Methods: Serum and bronchial wash samples were collected from patients undergoing diagnostic bronchoscopy. Total IgE, IgG and specific NTHi IgG were measured by enzyme linked immunosorbent assay. Bronchial wash samples were examined for the presence of NTHi via PCR. Results: Out of the 60 patients: 20 had confirmed Lung Cancer, 27 had COPD only and 13 were used as Controls. NTHi was detected in the lower airways of all three groups (Lung Cancer 20%; COPD 22% and Controls 15%). Total IgE was highest in Lung Cancer subjects followed by COPD and control subjects (mean ± SD: 870 ± 944, 381 ± 442, 159 ± 115). Likewise total IgG was higher in Lung cancer (Mean ± SD: 6.99 ± 1.8) patients compared to COPD (Mean ± SD: 5.43 ± 2). Conclusions: The lack of difference in NTHi and specific antibodies between the three groups makes it less likely that NTHi has an important pathogenetic role in subjects with Lung Cancer. However the detection of higher IgE antibody in Lung Cancer subjects identifies a possible mechanism for carcinogenesis in these subjects and warrants further study.
Delay and inequalities in the treatment of idiopathic pulmonary fibrosis: the case of two Nordic countries
Authors: Pesonen Ida , Carlson Lisa , Murgia Nicola , Kaarteenaho Riitta , Sköld Carl Magnus , Myllärniemi Marjukka , Murgia Giovanni
Published: January 2020

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive loss of lung function with high mortality within the first 5 years from diagnosis. In 2011–2014, two drugs, pirfenidone and nintedanib, have been approved worldwide for prevention of IPF progression. National IPF-registries have been established in both Finland and Sweden. Our study explored potential differences in the care of IPF in these two countries.
Methods: Patients included consecutively in the Finnish and Swedish IPF-registries from January 1, 2014 through December 31, 2016 were included in the study. Data on demographics and lung function at the time of inclusion were collected. Access to antifibrotic drugs and data on disease outcomes, mortality and the proportion of patients who underwent lung transplantation, was collected during a 3-year follow up.
Results: One-hundred and fifty-two patients from the Finnish and 160 patients from the Swedish IPF-cohorts were included in the study. At inclusion, Finnish patients were significantly older than the Swedish patients (74.6 years vs 72.5 years, p = 0.017). The proportion of non-smokers was significantly higher in the Finnish cohort (41.7% vs 26.9%, p = 0.007). Forced vital capacity (FVC), % of predicted (78.2 vs 71.7 for Finnish and Swedish patients, respectively, p = 0.01) and diffusion capacity for carbon monoxide (DLCO), % of predicted (53.3 vs 48.2 for Finnish and Swedish patients, respectively, p = 0.002) were significantly higher in the Finnish cohort compared to the Swedish cohort at the time of inclusion. During the 3-year follow up period, 45 (29.6%) Finnish and 111 (69.4%) Swedish patients, respectively, were initiated on treatment with an antifibrotic drug (pirfenidone or nintedanib) (p < 0.001). When comparing possible determinants of treatment, patients with higher FVC % were less likely to start antifibrotic drugs (OR 0.96, 95%CI 0.93–1.00, p < 0.024). To be resident in Sweden was the main determinant for receiving antifibrotic drugs (OR 5.48, 95%CI 2.65–11.33, p < 0.0001). No significant difference in number of deaths and lung transplantation during the follow up period was found.
Conclusions: This study highlights differences concerning how IPF patients are treated in Finland and Sweden. How these differences will influence the long-term outcome of these patients is unknown.
Correction to: Fluticasone furoate/Vilanterol 92/22 μg once-a-day vs Beclomethasone dipropionate/Formoterol 100/6 μg b.I.D.: a 12-month comparison of outcomes in mild-to-moderate asthma
Authors: Dal Negro Roberto W. , Bonadiman Luca , Turco Paola
Published: January 2020

Correction to: Multidisciplinary Respiratory Medicine (2018) 13:18 DOI: 10.1186/s40248-018-0131-x

After publication of the Original research article [1] it was brought to our attention that the sentence at pag 6 (between Fig. 3 and Fig. 4)) must be corrected as follows: “The mean duration of inactivity was 2.88 (0.63) at baseline; 1.53 (0.27) after 3; 1.40 (0.27) after 6, and 1.45 days (0.58) after twelve months (Anova: p = 0.11) in group A, while the corresponding duration in group B was 3.35 (0.63) at baseline; 0.60 (0.19) after 3; 1.10 (0.21) after 6, and 0.83 days (0.39) after 12 months (Anova; p <0.001), respectively.” In addition at pag. 7 Fig. 5 entitled “Changes in mean duration of inactivity/p. over 12 months” must be substituted with the new Fig. 5 because there is a mistake regarding anova p = 0.11 and consequently in the whole image. This Correction shows the revised Fig. 5. The original article has been updated.
State of the art in tracheal surgery: a brief literature review
Authors: Ibrahim Mohsen , Siciliani Alessandra , Rendina Erino Angelo
Published: January 2020

Background: Tracheal surgery requires a highly specialized team of anesthesiologists, thoracic surgeons, and operative support staff. It remain a formidable challenge for surgeons due to the criticality connected to anatomical considerations, intraoperative airway management, technical complexity of reconstruction, and the potential postoperative morbidity and mortality. Main body: This article focuses on the main technical aspects and literature data regarding laryngotracheal and tracheal resection and reconstruction. Particular attention will be paied to anastomotic and non-anastomotic complications. Short conclusion: Results from literature confirm that, when feasible, laryngotracheal and tracheal resection and reconstruction is the treatment of choice in cases of benign stricture and malign neoplasm. Careful patient selection, operative planning, and execution are required for optimal results.
Prevalence, risk factors, and impact of lung cancer on outcomes of idiopathic pulmonary fibrosis: a study from the Middle East
Authors: Mohamed Sherif , Bayoumi Hassan , El-Aziz Nashwa Abd , Mousa Ehab , Gamal Yasser
Published: January 2020

Background: No studies have addressed the impact of lung cancer (LC) on prognosis of patients with idiopathic pulmonary fibrosis (IPF) in Upper Egypt. We aimed to evaluate the prevalence and risk factors for LC among IPF patients and its impact on their outcomes and survival in Upper Egypt.
Methods: A total of 246 patients with IPF who had complete clinical and follow up data were reviewed. They were categorized into 2 groups: 34 patients with biopsy-proven LC and IPF (LC-IPF) and 212 patients with IPF only (IPF). Survival and clinical characteristics of the two groups were compared.
Results: Prevalence of LC was 13.8%. Pack/years was the most significant predictor for LC development in IPF (Odds ratio; 3.225, CI 1.257–1.669, p = 0.001). Survival in patients with LC-IPF was significantly worse than in patients with IPF without LC; median survival, 35 months vs 55 months; p = 0.000. LC accompanying IPF was one of the most significant independent predictors of survival in IPF patients (Hazard ratio 5.431, CI 2.186–13.492, p = 0.000). Mortality in LC-IPF patients was mainly due to LC progression in 36% and LC therapy-related complications in 22%.
Conclusions: Prevalence of LC in IPF patients was 13.8%. Lung cancer has significant impacts on patients with IPF in Upper Egypt, in terms of clinical outcomes and survival. Smoking is the most significant independent predictor of LC development in IPF patients. A poorer survival was observed for patients with IPF developing LC, mainly due to LC progression, and to complications of its therapies. Further prospective, multicenter and larger studies are warranted.
From CPAP to tailored therapy for obstructive sleep apnoea
Authors: Cistulli Peter A. , Sutherland Kate , Kairaitis Kristina , Yee Brendon J.
Published: January 2020

Obstructive Sleep Apnoea (OSA) is a common sleep disorder that is associated with daytime symptoms and a range of comorbidity and mortality. Continuous Positive Airway Pressure (CPAP) therapy is highly efficacious at preventing OSA when in use and has long been the standard treatment for newly diagnosed patients. However, CPAP therapy has well recognised limitations in real world effectiveness due to issues with patient acceptance and suboptimal usage. There is a clear need to enhance OSA treatment strategies and options. Although there are a range of alternative treatments (e.g. weight loss, oral appliances, positional devices, surgery, and emerging therapies such as sedatives and oxygen), generally there are individual differences in efficacy and often OSA will not be completely eliminated. There is increasing recognition that OSA is a heterogeneous disorder in terms of risk factors, clinical presentation, pathophysiology and comorbidity. Better characterisation of OSA heterogeneity will enable tailored approaches to therapy to ensure treatment effectiveness. Tools to elucidate individual anatomical and pathophysiological phenotypes in clinical practice are receiving attention. Additionally, recognising patient preferences, treatment enhancement strategies and broader assessment of treatment effectiveness are part of tailoring therapy at the individual level. This review provides a narrative of current treatment approaches and limitations and the future potential for individual tailoring to enhance treatment effectiveness.
Case finding of Alpha-1 antitrypsin deficiency: never wasted time!
Authors: Balbi Bruno
Published: January 2020

Alpha-1 Antitrypsin Deficiency (AATD) is considered the most important genetic cause of respiratory disorders, mainly COPD in its emphysematous phenotype. In high risk populations, [...]
Role of blood glucose and fat profile in lung function pattern of Indian type 2 diabetic subjects
Authors: Khafaie Morteza A. , Salvi Sundeep S. , Yajnik Chittaranjan S. , Rahim Fakher , Khafaei Behzad
Published: January 2020

Background and objectives: It has been hypothesized that changes in lung function can occur in patients with diabetes. Nevertheless, it is unclear how much of this correlation links with biomarkers of metabolism disorder. We have investigated the association between hypoglycaemic and fat profile with lung function in Indian diabetic subjects. Design: Prospective observational study. Setting: Diabetes care unit of King Edward Memorial (KEM) hospital. Patients: Out of 465 patients who agreed to participate in this study, valid lung function data were available from 347 Type 2 diabetic subjects. Measurements: Pulmonary function test including predicted forced vital capacity (% FVC), predicted forced expiratory volume in 1 second (% FEV1) and FEV1/FVC ratio were assessed. We also examined fat profile, glucose, HbA1c, hemoglobin and other hematological parameters. Results: Four hundred sixty-five subjects aged 55 ± 11 participated in the study. Predicted forced vital capacity, % FEV1 and FEV1/FVC ratio was 85.88 ± 13.53, 85.87 ± 14.06 and 82.03 ± 6.83, respectively. Also, approximately 8 to 17% of the participant reported having at least one chronic respiratory symptom or lung disease. We found that high glycaemic measures (i.e. fasting and post-meal plasma glucose) are linked with dyspnea. In addition, HDL (high-density lipoprotein) concentration was directly associated with % FVC. Conclusions: It is difficult to draw a clear conclusion about the cause-effect relationship or clinical impact based on this study alone. However, identification of clinically meaningful elements for developing a screening program is critical.
Diagnosing COPD in primary care: what has real life practice got to do with guidelines?
Authors: Ragaišienė Greta , Kibarskytė Rūta , Gauronskaitė Rasa , Giedraitytė Monika , Dapšauskaitė Agnė , Kasiulevičius Vytautas , Danila Edvardas
Published: January 2020

Background: The role of primary care physician in COPDmanagement varies in different health care systems. According to the researches in various countries, extent of spirometry use in diagnosing and grading COPD frequently remains insufficient. Inaccurate diagnosis results in mistreatment and disease progression. The aims of our study were to investigate the accuracy of COPD diagnosis, grading, and treatment according to guidelines in daily practice of primary care. Methods: A retrospective analysis of ambulatory records in a large primary care center was conducted. Digital medical records of current patients were screened for ICD-10-AM codes J44.0, J44.1, J44.8 and J44.9. All medical records starting from the first visit in this primary care center were reviewed. Results: Two hundred twenty-eight patients diagnosed with COPD were included in the study, 118 male, mean age 67 yrs. (SD 14). A spirometry report was available to 58% of the patients, 75% of them met the guidelines for COPD diagnosis. The grade was correct for 56.8% of the patients. 54% were consulted by the pulmonologist at least once. After re-analyzing spirometry, correcting the diagnosis, and grading, it was determined that only 70% of the patients were receiving appropriate treatments. Sixteen per cent of patients were undertreated and 14% were overtreated. Conclusions: COPD care in primary practice remains suboptimal. Incorrect approach often leads to incorrect grading and mistreatment. Points for improvement should be identified in further studies.
The Proceedings of the 16th Italian Convention of Investigators in Cystic Fibrosis
Authors: VV AA
Published: January 2020

Every year, the Italian Cystic Fibrosis Research Foundation (FFC) brings together all its funded researchers from across Italy and beyond, in a Convention where results from FFC projects are shared and debated. These projects are either newly funded, on-going or recently concluded research. The Proceedings of the 16th Convention of Italian Investigators in Cystic Fibrosis is a supplement of Multidisciplinary Respiratory Medicine reporting results of completed projects which were presented at the FFC 2018 Convention.
Observational vignette study to examine patient and healthcare provider perceived impact of asthma-related exacerbations in the US
Authors: Johnson Phaedra T. , Bell Christopher F. , White John , Essoi Breanna , Nelsen Linda , Averell Carlyne M.
Published: January 2020

Background: Little is known about how patients and healthcare providers (HCPs) perceive the impact of asthmarelated exacerbations. This study examined the impact of asthma-related exacerbations on patients’ lives from these different perspectives. Methods: Web-based surveys were administered to a US sample of adult patients with asthma, and HCPs. Participants reviewed six vignettes describing two hypothetical patients with asthma (25-year-old/single/unemployed/ no dependents; and 45-year-old/married/employed/two young children) experiencing mild, moderate, or severe exacerbations and rated the impact on eight measures: EuroQoL-5 Dimensions (mobility, self-care, usual activities, pain/ discomfort, and anxiety/depression), sleep, household costs, and medical costs. The proportions reporting impact for each measure were calculated for each vignette; and patient responses were compared with HCP responses. Results: 302 patients with asthma and 300 HCPs completed the survey. As exacerbation severity increased, a higher proportion of patients and HCPs reported impact of exacerbations on patients with asthma. Compared with HCPs, a greater proportion of patients reported problems with pain/discomfort related to mild and moderate exacerbations. Compared with patients, HCPs were more likely to indicate sleep impact, mobility problems, and financial burden across all exacerbation severity levels; self-care problems with moderate and severe exacerbations; and problems with usual activities and anxiety/depression for severe exacerbations. Conclusions: Understanding the distinctions between how patients and HCPs perceive the impact of exacerbations is important for optimizing patient care. HCPs may be less aware of patient’s concerns about exacerbation-related pain/ discomfort. Studies are needed to further understand patient-HCP interactions regarding asthma-related exacerbations.
Idiopathic pulmonary fibrosis: prognostic impact of histologic honeycombing in transbronchial lung cryobiopsy
Authors: Ravaglia Claudia , Bosi Marcello , Wells Athol U. , Gurioli Carlo , Gurioli Christian , Dubini Alessandra , Piciucchi Sara , Puglisi Silvia , Mascetti Susanna , Arcadu Antonella , Tomassetti Sara , Poletti Venerino
Published: January 2020

Background: Prognostic evaluation in idiopathic pulmonary fibrosis (IPF) may be important as it can guide management decisions, but the potential role of honeycomb changes in providing information about outcome and survival of patients with IPF, particularly if diagnosed using cryobiopsy, has not been evaluated. Aim of this study was to determinate whether a relationship exists between honeycombing on cryobiopsy and clinical/radiological picture and outcome in patients with IPF and to assess whether the same pathologic criteria that have been used to define the UIP pattern (usual interstitial pneumonia) for surgical biopsy can also be applied to cryobiopsy. Methods: Sixty-three subjects with a multidisciplinary diagnosis of IPF and a UIP pattern on cryobiopsy were evaluated. Patients were classified into two sub-groups depending on the presence of honeycombing on histology. Results: The presence of honeycombing on cryobiopsy did not identify a specific phenotype of patients as it did not correlate with radiological and clinical picture and it was not associated neither with the risk of death (p = 0. 1192) or with the event-free survival (p = 0.827); a higher number of samples and the presence of pleura on biopsy were instead associated with an increase in the finding of honeycombing. Conclusions: The same pathologic criteria that have been used to define the UIP pattern in surgical biopsies (with honeycombing changes considered as non-mandatory for the definition of the pattern itself) can be applied to cryobiopsy samples, as the presence of these changes do not define different clinical or radiological phenotypes of patients with IPF.