The role of non-invasive modalities for assessing inflammation in patients with non-cystic fibrosis bronchiectasis.

INTRODUCTION: Bronchiectasis is a heterogeneous entity, taking into account clinical characteristics, inflammatory response, effectiveness of treatment and frequency of exacerbations. In stable state non-cystic fibrosis (non-CF) bronchiectasis, little is known about non-invasive techniques used for evaluating airway inflammation in obstructive airway diseases. OBJECTIVES: We sought to evaluate the associations between induced sputum and clinical/radiologic characteristics, and the differences between biomarkers expressing Th1 and Th2 response in patients with non-CF bronchiectasis and to compare our findings with a previously studied population of patients with asthma and COPD. METHODS: We evaluated prospectively collected data from subjects with bronchiectasis. Comparisons were made between clinical, radiographic and physiologic characteristics, as well as induced sputum markers using appropriate statistical tools. We compared the levels of sputum markers with those of a previously studied cohort of asthma and COPD patients. RESULTS: We enrolled 40 subjects (21men, mean age 63.5yrs) with bronchiectasis. Fifteen subjects (37.5%) had a neutrophilic phenotype, 7 (17.5%) had an eosinophilic phenotype, 3 (12.5%) had a mixed neutrophilic-eosinophilic phenotype and 15 (37.5%) had a paucigranulocytic phenotype. Subjects with sputum neutrophilia had more severe bronchiectasis in HRCT and higher levels of IL-8 in sputum, whereas subjects with eosinophilia had higher levels of FeNO, greater bronchodilator reversibility and higher sputum IL-13. Sputum IL-8 levels were higher in subjects exhibiting frequent exacerbations and correlated with neutrophils in sputum (r=0.799), the extent of bronchiectasis in HRCT (r=0.765) and post-bronchodilator FEV1 (r=-0.416). Sputum IL-13 levels correlated with sputum eosinophils (r=0.656) and bronchodilator reversibility (r=0.441). Neutrophilic bronchiectasis exhibited comparable IL-8 levels to COPD, whereas eosinophilic bronchiectasis showed significantly lower IL-13 levels compared to asthma. CONCLUSIONS: Sputum cell counts and IL-8 and IL-13 correlate with distinct clinical and functional measurements of disease severity and therefore may have a role for non-invasively assessing inflammation in non-cystic fibrosis bronchiectasis.

Gaining access to the periphery of the lung: Bronchoscopic and transthoracic approaches.

Globally, lung cancer remains the leading cause of cancer-related death. Annual low-dose computed tomography has been recommended as a screening test for early detection of lung cancers. Implementing this screening strategy is expected to challenge pulmonologist to confirm the nature of the increasing number of detected pulmonary nodules. Clinicians are obliged to use the less invasive and most efficient and safe means to set diagnoses. Hence, the field of diagnostic modalities, especially the advanced diagnostic bronchoscopy is witnessing rapid evolution to fulfill these unmet needs. This review highlights the available diagnostic modalities, describes their advantages and discusses the limitations of each technique. It also suggests an integrated diagnostic algorithm based on the best available evidence. A search of the PubMed database was conducted using relevant terms described at methodology; only articles in English were reviewed by November 2016.

Effect of pulmonary rehabilitation on tidal expiratory flow limitation at rest and during exercise in COPD patients.

We hypothesized that severe COPD patients who present with the disadvantageous phenomenon of Expiratory Flow Limitation (EFL) may benefit as COPD patients without EFL do after implementation of a Pulmonary Rehabilitation (PR) program. Forty-two stable COPD patients were studied at rest and during exercise. EFL and dynamic hyperinflation (DH) were documented using the negative expiratory pressure (NEP) technique and inspiratory capacity (IC) maneuvers, respectively. Patient centered outcomes were evaluated by the Saint-George's Respiratory Questionnaire (SGRQ) and the mMRC dyspnea scale. Before PR, 16 patients presented with EFL at rest and/or during exercise. After PR, EFL was abolished in 15 out of those 16 EFL patients who exhibited a significant increase in IC values. These were mainly accomplished through a modification of the breathing pattern. In the 26 NFL patients no increase was noted in their IC or a modification of their breathing pattern. However, both NFL and EFL COPD patients improved exercise capacity and patients centered outcomes undergoing the same PR program.

Dyspnea and respiratory muscle strength in end-stage liver disease.

AIM: To investigate the prevalence of chronic dyspnea and its relationship to respiratory muscle function in end-stage liver disease. METHODS: Sixty-eight consecutive, ambulatory, Caucasian patients with end-stage liver disease, candidates for liver transplantation, were referred for preoperative respiratory function assessment. Forty of these (29 men) were included in this preliminary study after applying strict inclusion and exclusion criteria. Seventeen of 40 patients (42%) had ascites, but none of them was cachectic. Fifteen of 40 patients (38%) had a history of hepatic encephalopathy, though none of them was symptomatic at study time. All patients with a known history and/or presence of co-morbidities were excluded. Chronic dyspnea was rated according to the modified medical research council (mMRC) 6-point scale. Liver disease severity was assessed according to the Model for end-stage liver disease (MELD). Routine lung function tests, maximum static expiratory (Pemax) and inspiratory (Pimax) mouth pressures were measured. Respiratory muscle strength (RMS) was calculated from Pimax and Pemax values. In addition, arterial blood gases and pattern of breathing (VE: minute ventilation; VT: tidal volume; VT/TI: mean inspiratory flow; TI: duration of inspiration) were measured. RESULTS: Thirty-five (88%) of 40 patients aged (mean ± SD) 52 ± 10 years reported various degrees of chronic dyspnea (mMRC), ranging from 0 to 4, with a mean value of 2.0 ± 1.2. MELD score was 14 ± 6. Pemax, percent of predicted (%pred) was 105 ± 35, Pimax, %pred was 90 ± 29, and RMS, %pred was 97 ± 30. These pressures were below the normal limits in 12 (30%), 15 (38%), and 14 (35%) patients, respectively. Furthermore, comparing the subgroups of ascites to non-ascites patients, all respiratory muscle indices measured were found significantly decreased in ascites patients. Patients with ascites also had a significantly worse MELD score compared to non-ascites ones (P = 0.006). Significant correlations were found between chronic dyspnea and respiratory muscle function indices in all patients. Specifically, mMRC score was significantly correlated with Pemax, Pimax, and RMS (r = -0.53, P < 0.001; r = -0.42, P < 0.01; r = -0.51, P < 0.001, respectively). These correlations were substantially closer in the non-ascites subgroup (r = -0.82, P < 0.0001; r = -0.61, P < 0.01; r = -0.79, P < 0.0001, respectively) compared to all patients. Similar results were found for the relationship between mMRC vs MELD score, and MELD score vs respiratory muscle strength indices. In all patients the sole predictor of mMRC score was RMS (r = -0.51, P < 0.001). In the subgroup of patients without ascites this relationship becomes closer (r = -0.79, P < 0.001), whilst this relationship breaks down in the subgroup of patients with ascites. The disappearance of such a correlation may be due to the fact that ascites acts as a "confounding" factor. PaCO2 (4.4 ± 0.5 kPa) was increased, whereas pH (7.49 ± 0.04) was decreased in 26 (65%) and 34 (85%) patients, respectively. PaO2 (12.3 ± 0.04 kPa) was within normal limits. VE (11.5 ± 3.5 L/min), VT (0.735 ± 0.287 L), and VT/TI (0.449±0.129 L/s) were increased signifying hyperventilation in both subgroups of patients. VT/TI was significantly higher in patients with ascites than without ascites. Significant correlations, albeit weak, were found for PaCO2 with VE and VT/TI (r = -0.44, P < 0.01; r = -0.41, P < 0.01, respectively). CONCLUSION: The prevalence of chronic dyspnea is 88% in end-stage liver disease. The mMRC score closely correlates with respiratory muscle strength.

Methods for Assessing Expiratory Flow Limitation during Tidal Breathing in COPD Patients.

Patients with severe COPD often exhale along the same flow-volume curve during quite breathing as during forced expiratory vital capacity manoeuvre, and this has been taken as indicating expiratory flow limitation at rest (EFL(T)). Therefore, EFL(T), namely, attainment of maximal expiratory flow during tidal expiration, occurs when an increase in transpulmonary pressure causes no increase in expiratory flow. EFL(T) leads to small airway injury and promotes dynamic pulmonary hyperinflation with concurrent dyspnoea and exercise limitation. In fact, EFL(T) occurs commonly in COPD patients (mainly in GOLD III and IV stage) in whom the latter symptoms are common. The existing up-to-date physiological methods for assessing expiratory flow limitation (EFL(T)) are reviewed in the present work. Among the currently available techniques, the negative expiratory pressure (NEP) has been validated in a wide variety of settings and disorders. Consequently, it should be regarded as a simple, non invasive, most practical, and accurate new technique.

Effects of exercise-induced arterial hypoxaemia and work rate on diaphragmatic fatigue in highly trained endurance athletes.

Diaphragmatic fatigue occurs in highly trained athletes during exhaustive exercise. Since approximately half of them also exhibit exercise-induced arterial hypoxaemia (EIAH) during high-intensity exercise, the present study sought to test the hypothesis that arterial hypoxaemia contributes to exercise-induced diaphragmatic fatigue in this population. Ten cyclists ( : 70.0 +/- 1.6 ml kg(-1) min(-1); mean +/-s.e.m.) completed, in a balanced ordering sequence, one normoxic (end-exercise arterial O(2) saturation (S(a,O(2))): 92 +/- 1%) and one hyperoxic (F(I,O(2)): 0.5% O(2); S(a,O(2)) : 97 +/- 1%) 5 min exercise test at intensities equal to 80 +/- 3 and 90 +/- 3% of maximal work rate (WR(max)), respectively, producing the same tidal volume (V(T)) and breathing frequency (f) throughout exercise. Cervical magnetic stimulation was used to determine reduction in twitch transdiaphragmatic pressure (P(di,tw)) during recovery. Hyperoxic exercise at 90% WR(max) induced significantly (P= 0.022) greater post-exercise reduction in P(di,tw) (15 +/- 2%) than did normoxic exercise at 80% WR(max) (9 +/- 2%), despite the similar mean ventilation (123 +/- 8 and 119 +/- 8 l min(-1), respectively), breathing pattern (V(T): 2.53 +/- 0.05 and 2.61 +/- 0.05 l, f: 49 +/- 2 and 46 +/- 2 breaths min(-1), respectively), mean changes in P(di) during exercise (37.1 +/- 2.4 and 38.2 +/- 2.8 cmH(2)O, respectively) and end-exercise arterial lactate (12.1 +/- 1.4 and 10.8 +/- 1.1 mmol l(-1), respectively). The difference found in diaphragmatic fatigue between the hyperoxic (at higher leg work rate) and the normoxic (at lower leg work rate) tests suggests that neither EIAH nor lactic acidosis per se are likely predominant causative factors in diaphragmatic fatigue in this population, at least at the level of S(a,O(2)) tested. Rather, this result leads us to hypothesize that blood flow competition with the legs is an important contributor to diaphragmatic fatigue in heavy exercise, assuming that higher leg work required greater leg blood flow.

Effects of positive end-expiratory pressure on gas exchange and expiratory flow limitation in adult respiratory distress syndrome.

OBJECTIVE: To assess the effects of different positive end-expiratory pressure (PEEP) levels (0, 5, 10, and 15 cm H2O) on tidal expiratory flow limitation (FL), regional intrinsic positive end-expiratory pressure (PEEPi) inhomogeneity, alveolar recruited volume (Vrec), respiratory mechanics, and arterial blood gases in mechanically ventilated patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit of a university hospital. PATIENTS: Thirteen sedated, mechanically ventilated patients during the first 2 days of ARDS. INTERVENTIONS: Detection of tidal FL and evaluation of total dynamic PEEP (PEEPt,dyn), total static PEEP (PEEPt,st), respiratory mechanics, and Vrec from pressure, flow, and volume traces provided by the ventilator. The average (+/-sd) tidal volume was 7.1 +/- 1.5 mL/kg, the total cycle duration was 2.9 +/- 0.45 secs, and the duty cycle was 0.35 +/- 0.05. MEASUREMENTS: Tidal FL was assessed using the negative expiratory pressure technique. Regional PEEPi inhomogeneity was assessed as the ratio of PEEPt,dyn to PEEPt,st (PEEPi inequality index), and Vrec was quantified as the difference in lung volume at the same airway pressure between quasi-static inflation volume-pressure curves on zero end-expiratory pressure (ZEEP) and PEEP. RESULTS: On ZEEP, seven patients exhibited FL amounting to 31 +/- 8% of tidal volume. They had higher PEEPt,st and PEEPi,st ( p<.001) and lower PEEPi inequality index ( p<.001) than the six nonflow-limited (NFL) patients. Two FL patients became NFL with PEEP of 5 cm H2O and five with PEEP of 10 cm H2O. In both groups, PaO2 increased progressively with PEEP. In the FL group, there was a significant correlation of PaO2 to PEEPi inequality index ( p=.002). For a given PEEP, Vrec was greater in NFL than FL patients, and a significant correlation of Pao to Vrec ( p<.001) was found only in the NFL group. CONCLUSIONS: We conclude that on ZEEP, tidal FL is common in ARDS patients and is associated with greater regional PEEPi inhomogeneity than in NFL patients. With PEEP of 10 cm H2O, flow limitation with concurrent cyclic dynamic airway compression and re-expansion and the risk of "low lung volume injury" were absent in all patients. In FL patients, PEEP induced a significant increase in PaO2, mainly because of the reduction of regional PEEPi inequality, whereas in the NFL group, arterial oxygenation was improved satisfactorily because of alveolar recruitment.