Inhaled high molecular weight hyaluronan ameliorates respiratory failure in acute COPD exacerbation: a pilot study.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) carry significant morbidity and mortality. AECOPD treatment remains limited. High molecular weight hyaluronan (HMW-HA) is a glycosaminoglycan sugar, which is a physiological constituent of the lung extracellular matrix and has notable anti-inflammatory and hydrating properties. RESEARCH QUESTION: We hypothesized that inhaled HMW-HA will improve outcomes in AECOPD. METHODS: We conducted a single center, randomized, placebo-controlled, double-blind study to investigate the effect of inhaled HMW-HA in patients with severe AECOPD necessitating non-invasive positive-pressure ventilation (NIPPV). Primary endpoint was time until liberation from NIPPV. RESULTS: Out of 44 screened patients, 41 were included in the study (21 for placebo and 20 for HMW-HA). Patients treated with HMW-HA had significantly shorter duration of NIPPV. HMW-HA treated patients also had lower measured peak airway pressures on the ventilator and lower systemic inflammation markers after liberation from NIPPV. In vitro testing showed that HMW-HA significantly improved mucociliary transport in air-liquid interface cultures of primary bronchial cells from COPD patients and healthy primary cells exposed to cigarette smoke extract. INTERPRETATION: Inhaled HMW-HA shortens the duration of respiratory failure and need for non-invasive ventilation in patients with AECOPD. Beneficial effects of HMW-HA on mucociliary clearance and inflammation may account for some of the effects (NCT02674880, www.clinicaltrials.gov ).

Bone fragility in patients with diabetes mellitus: A consensus statement from the working group of the Italian Diabetes Society (SID), Italian Society of Endocrinology (SIE), Italian Society of Gerontology and Geriatrics (SIGG), Italian Society of Orthopaedics and Traumatology (SIOT).

Bone fragility is one of the possible complications of diabetes, either type 1 (T1D) or type 2 (T2D). Bone fragility can affect patients of different age and with different disease severity depending on type of diabetes, disease duration and the presence of other complications. Fracture risk assessment should be started at different stages in the natural history of the disease depending on the type of diabetes and other risk factors. The risk of fracture in T1D is higher than in T2D, imposing a much earlier screening and therapeutic intervention that should also take into account a patient's life expectancy, diabetes complications etc. The therapeutic armamentarium for T2D has been enriched with drugs that may influence bone metabolism, and clinicians should be aware of these effects. Considering the complexity of diabetes and osteoporosis and the range of variables that influence treatment choices in a given individual, the Working Group on bone fragility in patients with diabetes mellitus has identified and issued recommendations based on the variables that should guide screening of bone fragility and management of diabetes and bone fragility: (A)ge, (B)MD, (C)omplications, (D)uration of disease, & (F)ractures (ABCD&F). Consideration of these parameters may help clinicians identify the best time for screening, the appropriate glycaemic target and anti-osteoporosis drug for patients with diabetes at risk of or with bone fragility.

Gas exchanges and pulmonary vascular abnormalities at different stages of chronic liver disease.

BACKGROUND: It is unclear whether and to which extent respiratory function abnormalities may complicate the earliest stages of chronic liver disease (CLD). Aim of this study was to compare pulmonary capillary volumes and gas exchange efficiency of CLD patients with and without cirrhosis. METHODS: Sixty-seven participants (mean age 56.5 years; women 22.4%) were divided into three groups (matched by age, sex, smoking) according to the baseline CLD stage as follows: (a) healthy controls (Group A, n=20); (b) non-cirrhotic CLD patients (Group B; n=23); (c) cirrhotic CLD patients (Group C; n=24). All participants underwent clinical assessment, respiratory function tests, gas exchange estimation by the alveolar diffusion of carbon monoxide (TLCO) measurement and 6-min walking test. Groups were compared by chi-square and one-way anova tests. RESULTS: Chronic liver disease patients had significantly lower levels of TLCO (Group B=17.7 ml/min mmHg, and Group C=14.2 ml/min mmHg) compared with healthy controls (Group A=24.4 ml/min mmHg). Consistent results were obtained when analyses were performed using TLCO expressed as percentage of the predicted value. TLCO adjusted for the alveolar volume was lower in cirrhotic patients compared with both controls and non-cirrhotic CLD patients (P<0.001 and P=0.035 respectively). Group C participants presented blood gas parameters tending to a compensated chronic respiratory alkalosis status compared with the other groups. CONCLUSIONS: Pulmonary microvascular and gas exchange modifications are present at early stages of CLD. Future studies should be focused at evaluating the pathophysiological mechanisms underlying this relationship.

Valsalva maneuver in phlebologic practice.

Forced expiration against an airway obstruction was originally described as a method for inflating the Eustachian tubes and is accredited to Antonio Maria Valsalva (1666-1723). The Valsalva maneuver is commonly applied for different diagnostic purposes. Its use for phlebologic diagnosis is the object this review. Venous reflux is the most frequent pathophysiologic mechanism in chronic venous disease. Reflux is easily visualized by duplex ultrasound when properly elicited, in standing position. A simple way to elicit reflux is the so-called "compression-release maneuver": by emptying the muscle reservoir, it determines a centrifugal gradient, dependent on hydrostatic pressure, creating an aspiration system from the superficial to the deep system. The same results are obtained with dynamics tests activating calf muscles. The Valsalva maneuver elicits reflux by a different mechanism, increasing the downstream pressure and, thus, highlighting any connection between the source of reflux and the refluxing vessel. The Valsalva maneuver is typically used to investigate the saphenofemoral junction. When the maneuver is performed correctly, it is very useful to analyse several conditions and different hemodynamic behaviours of the valvular system at the saphenofemoral junction. Negative Valsalva maneuver always indicates valvular competence at the saphenofemoral junction. Reverse flow lasting during the whole strain (positive Valsalva maneuver) indicates incompetence or absence of proximal valves. Coupling Valsalva maneuver to compression-release maneuver, with the sample volume in different saphenofemoral junction sections, may reveal different hemodynamic situations at the saphenofemoral junction, which can be analysed in detail.

Sleep quality disturbances and cognitive functioning in elderly patients with COPD.

Information about the association between cognitive functions, such as copying function, and sleep disturbances in patients with chronic obstructive pulmonary disease (COPD) is lacking. This cross-sectional observational study aimed to investigate the association between copying function and self-reported sleep quality disturbances and disease severity in an elderly COPD population. Cognitive function performances, assessed using the Mini-Mental State Examination, were compared in 562 ambulatory COPD patients with and without sleep disturbances; assessed using the Established Populations for Epidemiologic Studies of the Elderly questionnaire; and stratified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades. Sleep disturbances overall were not correlated with cognitive functioning. A trend was revealed towards worse design copying in patients with sleep disturbances overall. GOLD I patients with difficulties falling asleep and nocturnal awakenings had worse copying ability compared to GOLD I patients without these sleep disturbances. Copying ability was worse for GOLD III than GOLD I, orientation was worse for GOLD II than GOLD I and language was worse for GOLD II and III than GOLD I. To conclude, sleep disturbances seem to be a weak correlate of cognitive functioning, and are not a marker of disease severity.

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.