Reference equations for within-breath respiratory oscillometry in White adults.

BACKGROUND: within-breath analysis of oscillometry parameters is a growing research area since it increases sensitivity and specificity to respiratory pathologies and conditions. However, reference equations for these parameters in White adults are lacking and devices using multiple sinusoids or pseudorandom forcing stimuli have been underrepresented in previous studies deriving reference equations. The current study aims to establish reference ranges for oscillometry parameters, including also the within-breath ones in White adults using multi-sinusoidal oscillations. METHODS: White adults with normal spirometry, BMI≤30kg/m2, without a smoking history, respiratory symptoms, pulmonary or cardiac disease, neurological or neuromuscular disorders, and respiratory tract infections in the previous 4 weeks were eligible for the study. Study subjects underwent oscillometry (multifrequency waveform at 5-11-19Hz, Resmon PRO FULL, Restech Srl, Italy) in 5 centers in Europe and the USA according to international standards. The within-breath and total resistance (R) and reactance (X), the resonance frequency, the area under the X curve, the frequency dependence of R (R5-19), and within-breath changes of X (ΔX) were submitted to Lambda-Mu-Sigma models for deriving reference equations. For each output parameter, an AIC-based stepwise input variable selection procedure was applied. RESULTS: 144 subjects (age 20.8 - 86.3 years; height 146 - 193 cm; BMI 17.42 - 29.98 kg/m2; 56% females) were included. We derived reference equations for 29 oscillatory parameters. Predicted values for inspiratory and expiratory parameters were similar, while differences were observed for their limits of normality. CONCLUSIONS: We derived reference equations with narrow confidence intervals for within-breath and whole-breath oscillatory parameters for White adults.

Molecular Testing in EBUS-TBNA Specimens of Lung Adenocarcinoma: A Study of Concordance Between Cell Block Method and Liquid-Based Cytology in Appraising Sample Cellularity and EGFR Mutations.

PURPOSE: Cytological endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimens of mediastinal lymph node metastasis are frequently used to perform concomitant diagnosis, staging and genetic testing in non-small-cell lung cancer (NSCLC). The purposes of this single-center retrospective study were to evaluate EBUS-TBNA samples' adequacy for molecular testing of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and to analyze the concordance between the cell block method and liquid-based cytology (LBC) in appraising the sample cellularity and in detecting EGFR mutation. MATERIALS AND METHODS: We retrospectively examined 82 patients who underwent EBUS-TBNA from October 2012 to September 2015 and received a confirmed diagnosis of lymph node metastasis of lung adenocarcinoma. Each sample was processed using both cell block and LBC to carry out DNA analysis (adequacy criterion: tumor cell percentage > 25%) and EGFR mutation testing. RESULTS: Fifty-four patients were male, 66 were current or former-smokers, and the median age was 67 years. The median size of sampled lymph nodes was 14.8 mm. Seventy-one and 66 samples were adequate to perform cell block and LBC, respectively. The κ-statistic (0.78) showed an excellent concordance. EGFR mutation was detected in eight patients using cell block and in seven using LBC, with a simple percentage agreement of 87.5%. ALK translocation was found in two patients. CONCLUSIONS: This study demonstrates the feasibility of EGFR mutation analysis with both cell block and LBC, with an excellent concordance between the two methods. Considering that the majority of advanced NSCLCs are diagnosed on cytology specimens, LBC is feasible and needs to be implemented for ancillary tests (immunocytochemistry, molecular analysis).

Ultrasonography of the Mediastinum: Techniques, Current Practice, and Future Directions.

In the everyday practice of respiratory physicians, ultrasound techniques play a key role by enabling several diagnostic and interventional procedures. The application of ultrasound to endoscopic procedures allows both a visualization and a guided sampling of mediastinal and hilar lymph nodes. Endobronchial ultrasound can be combined with transbronchial needle aspiration, and, similarly, endoscopic ultrasound can be combined with fine-needle aspiration to sample virtually all mediastinal nodal stations from the airways and the esophagus. Endobronchial ultrasound-transbronchial needle aspiration and endoscopic ultrasound-fine needle aspiration showed a complementary diagnostic yield, and, recently, endoscopic ultrasound with bronchoscope was introduced in clinical practice to perform a transesophageal needle aspiration by using an ultrasound bronchoscope. This technique allows a single operator to perform both transbronchial and transesophageal needle sampling with the same instrument during a single bronchoscopic procedure. Mediastinal staging impacts the management of patients affected by lung cancer, and the most recent guidelines clearly state that endobronchial ultrasound and endoscopic ultrasound should be the initial tissue sampling procedure over surgical staging. In addition, endoscopic ultrasound techniques demonstrated an excellent yield in diagnosing lymphoma and benign diseases, for example, sarcoidosis. The aim of this review was to discuss the current role and future perspectives of endosonography techniques available for the evaluation of the mediastinum. Special emphasis was placed on equipment and technical aspects, the diagnostic role, and future directions of development.

Analysis of risk factors in the development of bronchopleural fistula after major anatomic lung resection: experience of a single centre.

BACKGROUND: The bronchopleural fistula (BPF) is a rare but potentially fatal complication of major thoracic surgery. The purpose of this work is to investigate the risk factors associated with the development of fistulas after lobectomy and pneumonectomy. METHODS: We retrospectively reviewed the records of 835 patients who underwent major anatomic lung resection at our centre from January 2003 to December 2013. Of these, 49 underwent pneumonectomy (P group) and 786 lobectomy (L group). RESULTS: A total of 18 patients (2.6%) developed a BPF in the postoperative period, of which there were 11 in the L group (1.3%) and seven in the P group (14.28%). The 30-day mortality was 0.05% (one patient after right pneumonectomy). In the L group, three patients developed a fistula after a left lobectomy and eight after a right one, of which four developed after bilobectomy. Univariate analysis showed that induction therapy, lower lobectomy, manual suture of the bronchus, 'not covered' bronchial stump, empyema, postoperative anaemia and pulmonary infections and mechanical ventilation >24 h are associated with the development of fistulas after lobectomy. Multivariate analysis confirmed that induction therapy, manual closure of the bronchus, postoperative pulmonary infections and anaemia are the main risk factors involved in our series. In the P group, four patients developed a fistula after a right pneumonectomy and three after a left one. Postoperative empyema and pulmonary infections, mechanical ventilation >24 h and female gender emerged as the main risk factors on univariate analysis, while on multivariate analysis, only the female gender presented a trend towards significance. CONCLUSIONS: Postoperative pulmonary infections, empyema and mechanical ventilation >24 h are strongly associated with the development of BPFs after both pneumonectomy and lobectomy in our series.

Influence of the Learning Effect on the Diagnostic Yield of Endobronchial Ultrasound-guided Transbronchial Needle Aspiration of Mediastinal and Hilar Lymph Nodes.

BACKGROUND: The diagnostic yield of conventional transbronchial needle aspiration (TBNA) is characterized by a learning effect. The aim of this retrospective study was to verify whether a learning curve similarly affected the yield of endobronchial ultrasound-guided (EBUS)-TBNA. To this end, we evaluated the sensitivity and diagnostic accuracy of EBUS-TBNA during the first 3 years of activity. METHODS: EBUS-TBNA was performed by 2 operators with no previous experience in this technique. Cytologic samples were obtained from mediastinal and hilar lymph nodes enlarged at a chest computed tomography scan and/or with increased fluorodeoxyglucose uptake at computed tomography/positron emission tomography scan in patients with suspected lung cancer. The cytologic diagnosis of EBUS-TBNA samples has been compared with the final diagnosis obtained from further diagnostic procedures, surgery, or clinical-radiologic follow-up. RESULTS: From October 2012 to October 2015, we collected 408 EBUS-TBNA cytologic samples from 313 patients: 223 samples were positive for metastatic involvement and 185 were nonmetastatic. The latter included 137 true-negative and 48 false-negative results. The final diagnosis comprised 271 metastatic and 137 nonmetastatic lymph nodes. The overall sensitivity for cancer was 82% and diagnostic accuracy was 88%. Sensitivity and accuracy per year were as follows: first year, 78% and 82% in 90 nodal samples; second year, 83% and 89% in 144 nodal samples; third year, 85% and 91% in 174 nodal samples. CONCLUSIONS: EBUS-TBNA can be considered as a reliable tool even if performed by operators without previous experience in this procedure, and the diagnostic yield continues to increase progressively over a long time.

Exhaled and non-exhaled non-invasive markers for assessment of respiratory inflammation in patients with stable COPD and healthy smokers.

We aimed at comparing exhaled and non-exhaled non-invasive markers of respiratory inflammation in patients with chronic obstructive pulmonary disease (COPD) and healthy subjects and define their relationships with smoking habit. Forty-eight patients with stable COPD who were ex-smokers, 17 patients with stable COPD who were current smokers, 12 healthy current smokers and 12 healthy ex-smokers were included in a cross-sectional, observational study. Inflammatory outcomes, including prostaglandin (PG) E2 and 15-F2t-isoprostane (15-F2t-IsoP) concentrations in exhaled breath condensate (EBC) and sputum supernatants, fraction of exhaled nitric oxide (FENO) and sputum cell counts, and functional (spirometry) outcomes were measured. Sputum PGE2 was elevated in both groups of smokers compared with ex-smoker counterpart (COPD: P < 0.02; healthy subjects: P < 0.03), whereas EBC PGE2 was elevated in current (P = 0.0065) and ex-smokers with COPD (P = 0.0029) versus healthy ex-smokers. EBC 15-F2t-IsoP, a marker of oxidative stress, was increased in current and ex-smokers with COPD (P < 0.0001 for both) compared with healthy ex-smokers, whereas urinary 15-F2t-IsoP was elevated in both smoker groups (COPD: P < 0.01; healthy subjects: P < 0.02) versus healthy ex-smokers. FENO was elevated in ex-smokers with COPD versus smoker groups (P = 0.0001 for both). These data suggest that the biological meaning of these inflammatory markers depends on type of marker and biological matrix in which is measured. An approach combining different types of outcomes can be used for assessing respiratory inflammation in patients with COPD. Large studies are required to establish the clinical utility of this strategy.

Incidence and Management of Post-Lobectomy and Pneumonectomy Bronchopleural Fistula.

INTRODUCTION: Bronchopleural fistula is a rare but potentially fatal complication of pulmonary resections and proper management is essential for its resolution. In this study, we analyzed the incidence of fistula after pulmonary resection and reported data about endoscopic and conservative treatments of this complication. METHODS: From January 2003 to December 2013, 835 patients underwent anatomic lung resections: 786 (94.1 %) had a lobectomy and 49 (5.9 %) a pneumonectomy. Bronchopleural fistula was suspected by clinical signs and confirmed by endoscopic visualization. RESULTS: Eighteen patients (2.2 %) developed a bronchopleural fistula, 11 in lobectomy group (1.4 %) and 7 in pneumonectomy group (14.3 %). The fistula size ranged between <1 mm and 6 mm and mean time of fistula onset was 33.9 ± 54.9 days after surgery. Of 18 patients who developed fistula, one died due to acute respiratory failure and another one was reoperated and then died to causes unrelated to the treatment. All the remaining 16 patients were treated with a conservative therapy that consisted in keeping or replacing a drainage chest tube. Nine of them underwent also endoscopic closure of the fistula using biological or synthetic glues. The mean period of time elapsed for the resolution of this complication was shorter with combined (conservative + endoscopic) than with conservative treatment alone (15.4 ± 13.2 vs. 25.8 ± 13.2 days, respectively), but without significant difference between the two methods (p: 0.299). CONCLUSION: Endoscopic therapy, associated with a conservative treatment, is a safe and useful option in the management of the postoperative bronchopleural fistula.

Usefulness of Conventional Transbronchial Needle Aspiration for Sampling of Mediastinal Lymph Nodes in Lung Cancer.

BACKGROUND: Transbronchial needle aspiration (TBNA) is recognized as a valuable tool for the sampling of mediastinal lymph nodes. In this study, we report data about the diagnostic yield of conventional TBNA in the diagnosis and staging of lung cancer. METHODS: All patients with suspected lung cancer who underwent bronchoscopy with conventional TBNA in the years 2008 to 2012 were evaluated. TBNA was performed on mediastinal lymph nodes enlarged at chest computed tomography scan and/or with increased fluorodeoxyglucose uptake on positron emission tomography/computed tomography scan. Cytologic results derived from TBNA have been compared, with the final diagnosis obtained with other more invasive procedures and/or with a clinical-radiologic follow-up of at least 12 months. RESULTS: TBNA was performed on 375 patients. However, 19 patients were lost to follow-up, and data from 356 patients with a total 459 TBNA specimens were analyzed. TBNA was positive for metastatic involvement of lymph nodes in 172 of 282 patients with cancer, with a sensitivity of 61%. Sensitivity achieved 65% when we considered the total of 459 TBNA specimens. The overall diagnostic accuracy of TBNA was 69%. The nodal stations more frequently examined were 7 (subcarinal: 190 TBNAs), 4R (right lower paratracheal: 147 TBNAs), and 10R (right hilar: 76 TBNAs), with a sensitivity of 66%, 66%, and 67%, respectively. CONCLUSION: Conventional TBNA remains a useful method for the diagnosis and staging of lung cancer, with a good diagnostic yield in several nodal stations.

Role of ultrasound-guided transbronchial biopsy in the diagnosis of peripheral pulmonary lesions.

INTRODUCTION: Endobronchial ultrasound (EBUS) can be used as an alternative to fluoroscopy to visualize a peripheral pulmonary lesion (PPL) and to provide an image guidance for transbronchial biopsy (TBB). The aim of this study was to verify the accuracy of EBUS-guided TBB in the diagnosis of PPLs. METHODS: All the patients with CT-scan evidence of PPL who underwent bronchoscopy with EBUS in the period between 2008 and 2011 were retrospectively evaluated. EBUS was performed using a radial-type miniature ultrasound probe. Once obtained an EBUS image of the PPL, we measured the distance of the PPL from the outer orifice of the working channel of the bronchoscope in order to perform TBB at PPL site. RESULTS: A total of 662 patients were examined. The mean diameter of lesions was 36 ± 20 mm. PPLs were visualized in 494 patients (75%) and the TBB was performed in 479 patients. Thirty-two patients were lost in follow-up and data from 447 patients were analyzed. TBB results were 255 cancers and 192 non-malignant lesions. The final diagnosis reported was 359 cases of cancer and 88 of benign lesion. EBUS-guided TBB had a sensitivity of 71% for the diagnosis of cancer, a negative predictive value of 46% and an overall diagnostic accuracy of 77%. CONCLUSIONS: These data obtained from a large series of patients and using an original method show that EBUS represents a valid support to bronchoscopy and that the EBUS-guided TBB has a high diagnostic yield in the diagnosis of PPLs.

Husband and wife with sarcoidosis: possible environmental factors involved.

Sarcoidosis is a granulomatous multisystem disorder of unclear etiology that involves any organ, most commonly the lung and the lymph nodes. It is hypothesized that the disease derives from the interaction between single or multiple environmental factors and genetically determined host factors. Multiple potential etiologic agents for sarcoidosis have been proposed without any definitive demonstration of causality.We report the case of two patients, husband (57 years old) and wife (55 years old), both suffering from sarcoidosis. They underwent a lymph node biopsy by mediastinoscopy which showed a "granulomatous epithelioid giant cell non-necrotising chronic lymphadenitis". They had lived up to 3 years ago in the country in a farm, in contact with organic dusts, animals such as dogs, chickens, rabbits, pigeons; now they have lived since about 3 years in an urban area where there are numerous chemical industries and stone quarries. The aim of this case report was to focus on environmental factors that might be related to the pathogenesis of the sarcoidosis.

The diabetic lung--a new target organ?

Several abnormalities of the respiratory function have been reported in patients with type 1 and type 2 diabetes. These abnormalities concern lung volume, pulmonary diffusing capacity, control of ventilation, bronchomotor tone, and neuroadrenergic bronchial innervation. Many hypotheses have emerged, and characteristic histological changes have been described in the "diabetic lung", which could explain this abnormal respiratory function. Given the specific abnormalities in diabetic patients, the lung could thus be considered as a target organ in diabetes. Although the practical implications of these functional changes are mild, the presence of an associated acute or chronic pulmonary and/or cardiac disease could determine severe respiratory derangements in diabetic patients. Another clinical consequence of the pulmonary involvement in diabetes is the accelerated decline in respiratory function. The rate of decline in respiratory function in diabetics has been found to be two-to-three times faster than in normal non-smoking subjects, as reported in longitudinal studies. This finding, together with the presence of anatomical and biological changes similar to those described in the aging lung, indicates that the "diabetic lung" could even be considered a model of accelerated aging. This review describes and analyses the current insight into the relationship of diabetes and lung disease, and suggests intensifying research into the lung as a possible target organ in diabetes.

Reduced respiratory muscle strength and endurance in type 2 diabetes mellitus.

BACKGROUND: A restrictive lung function pattern is frequently observed in patients with diabetes mellitus (DM) and has been related to respiratory muscle dysfunction in type 1 DM or in mixed population. We aimed to verify whether such a relationship applies also to type 2 DM patients. METHODS: The respiratory muscle function was explored in 75 non-smoking patients with type 2 DM without pulmonary or cardiac diseases and compared with that of 40 healthy non-smoking control subjects matched by age and sex. Maximal inspiratory and expiratory pressures (MIP, MEP) and maximum voluntary ventilation (MVV), which reflect respiratory muscle strength and endurance, respectively, were measured, and a complete respiratory function assessment was recorded. RESULTS: Patients were in stable metabolic conditions and had, on average, normal total lung capacity and diffusing lung capacity for carbon monoxide. However, MIP and MVV were significantly reduced in comparison with those of control subjects. Both MIP/MEP and MVV significantly correlated with lung volumes and diffusing lung capacity for carbon monoxide. The multiple regression analysis identified age (beta coefficient = -0.238, p = 0.046), glycated haemoglobin (beta coefficient = -0.245, p = 0.047) and total lung capacity (beta coefficient = 0.430, p = 0.016) as independent correlates of MIP, whereas male sex (beta coefficient = 0.423, p = 0.004) and diabetic complications (beta coefficient = -0.248, p = 0.044) were independent correlates of MVV. CONCLUSIONS: In type 2 DM, respiratory muscle strength was reduced and significantly related to lung volumes and quality of metabolic control, whereas impaired endurance of respiratory muscles prevailed in patients with microvascular complications.

Diagnosis of invasive aspergillosis by a commercial real-time PCR assay for Aspergillus DNA in bronchoalveolar lavage fluid samples from high-risk patients compared to a galactomannan enzyme immunoassay.

Culture-independent molecular techniques such as real-time PCRs offer the potential for early diagnosis of invasive aspergillosis (IA), thereby reducing the disease-associated mortality rate. PCR-based testing is presently excluded from disease-defining consensus criteria due to lack of standardization and clinical validation. A single-center prospective study was conducted to investigate the performance of the commercially available MycAssay Aspergillus test for detecting Aspergillus DNA in patients with suspicion of IA. To this end, a total of 158 bronchoalveolar lavage (BAL) fluid specimens that were consecutively collected from hematology (n = 68) and intensive care unit (n = 90) patients were examined. Sixteen of 17 (94.1%) specimens from patients with proven/probable IA were MycAssay positive, and 15 of these 16 patients were also positive by an "in-house" PCR assay. A total of 139 of 141 (98.6%) specimens from patients without proven/probable IA were MycAssay negative. Fifteen of 16 (94.1%) MycAssay-positive patients were also positive for BAL fluid galactomannan (GM) at an index cutoff of ≥1.0 (index range, 1.1 to 8.3), as were 3 patients without IA but with pulmonary fusariosis. Interestingly, in seven of the PCR-positive BAL specimens that tested culture positive for Aspergillus species, cycle threshold values were earlier than those of specimens with a culture-negative result. In conclusion, the MycAssay Aspergillus PCR appears to be a sensitive and specific molecular test for the diagnosis of IA, and its performance is comparable to that of the GM assay. However, more large studies are necessary to firmly establish its clinical utility in high-risk settings.