Physiology of respiratory disturbances in muscular dystrophies

Muscular dystrophy is a group of inherited myopathies characterised by progressive skeletal muscle wasting, including of the respiratory muscles. Respiratory failure, i.e. when the respiratory system fails in its gas exchange functions, is a common feature in muscular dystrophy, being the main cause of death, and it is a consequence of lung failure, pump failure or a combination of the two. The former is due to recurrent aspiration, the latter to progressive weakness of respiratory muscles and an increase in the load against which they must contract. In fact, both the resistive and elastic components of the work of breathing increase due to airway obstruction and chest wall and lung stiffening, respectively. The respiratory disturbances in muscular dystrophy are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. They can be present at different rates according to the type of muscular dystrophy and its progression, leading to different onset of each symptom, prognosis and degree of respiratory involvement

Assessment and management of respiratory function in patients with duchenne muscular dystrophy: Current and emerging options

Duchenne muscular dystrophy (DMD) is an X-linked myopathy resulting in progressive weakness and wasting of all the striated muscles including the respiratory muscles. The consequences are loss of ambulation before teen ages, cardiac involvement and breathing difficulties, the main cause of death. A cure for DMD is not currently available. In the last decades the survival of patients with DMD has improved because the natural history of the disease can be changed thanks to a more comprehensive therapeutic approach. This comprises interventions targeted to the manifestations and complications of the disease, particularly in the respiratory care. These include: 1) pharmacological intervention, namely corticosteroids and idebenone that significantly reduce the decline of spirometric parameters; 2) rehabilitative intervention, namely lung volume recruitment techniques that help prevent atelectasis and slows the rate of decline of pulmonary function; 3) scoliosis treatment, namely steroid therapy that is used to reduce muscle inflammation/degeneration and prolong ambulation in order to delay the onset of scoliosis, being an additional contribution to the restrictive lung pattern; 4) cough assisted devices that improve airway clearance thus reducing the risk of pulmonary infections; and 5) non-invasive mechanical ventilation that is essential to treat nocturnal hypoventilation, sleep disordered breathing, and ultimately respiratory failure. Without any intervention death occurs within the first 2 decades, however, thanks to this multidisciplinary therapeutic approach life expectancy of a newborn with DMD nowadays can be significantly prolonged up to his fourth decade. This review is aimed at providing state-of-the-art methods and techniques for the assessment and management of respiratory function in DMD patients

Blood shift during cough: Negligible or significant?

Rationale: It was reported how forceful rhythmic coughing can provide effective blood flow during ventricular fibrillation without direct chest compression. This mechanism of cough-assisted cardiopulmonary resuscitation constitutes a form of "cardiac massage" secondary to the intrathoracic and intra-abdominal pressure changes during cough. We have previously shown that significant blood shifts (BSs) occurs from the thorax to the extremities during expulsive maneuvers and that abdominal pressure controls the outflow of blood from the splanchnic vasculature. This mechanism was called abdominal circulatory pump. BS was quantified by using double body plethysmography (DBP), which combines total body plethysmography and opto-electronic plethysmography. Aim: We hypothesized that coughing activates also the abdominal circulatory pump, being an additional mechanism that displaces a circulatory output sufficient to maintain consciousness in a patient with a non-beating heart. Methods and Results: We studied seven healthy subjects (age: 28.6 ± 2.5 years) during series of voluntary coughs at three different operating volumes: after a spontaneous tidal volume, at total lung capacity (TLC) and at an intermediate volume. BS from the thorax to the extremities were measured by DBP during quiet breathing and during cough at each operating lung volume. BS during cough resulted significantly higher than during quiet breathing (p < 0.05). During the compressive phase, the blood outflow is around 200 ml, whereas during the expulsive phase BS increased (p < 0.05) with increasing operating volume, being almost 700 ml at TLC. At lower operating volume it is almost 400 ml. Conclusion: Deep, vigorous coughing and the consequent fluctuations in intra-thoracic and intra-abdominal pressure activate both the thoracic and the abdominal pump mechanism. The former leads the low-resistance pulmonary veins to empty into the left heart. The latter can generate a circulatory output from the splanchnic region, which acts as a blood reservoir, to other body tissues. These findings might help to better understand the cardiopulmonary interactions during cough, particularly in patients with unstable cardiac function, and the mechanism by which coughing during unstable cardiac rhythms can maintain consciousness in human subjects

Surveying, modeling and communication techniques for the documentation of medieval wooden painted ceilings in the Mediterranean area

Wooden painted ceilings of the Mediterranean area in the middle age have their origin in the islamic culture and were then spread in the countries under the dominion of the Arabs; some of the surviving ceilings are now located in Sicily and Spain. In the historic centre of Palermo two well preserved medieval ceilings are still surviving; the first, built in the XII century, is located in the Palatine chapel; the second one, built in the XIV century covers the “Sala Magna” in the Steri of Palermo. The research, focused on the ceiling in the Steri, deals with the definition of a process for the integration of surveying techniques (photogrammetry, laser scanning), modelling processes and communication technologies for the documentation of such artefacts. The documentation of painted ceilings requires the strict integration of photographic and 3D metric data; the existing documentation is usually made of documents (drawings, photographs) that keep geometric and metric data separated from the photographic documentation of the paintings. The first stage in this work is therefore addressed to produce a digital document that combines metric and photographic data in a 3D textured model; in the second stage a vocal guide interacting with the 3D model has been developed; such guide, thought as a support to people visiting the Steri, uses a database with historic contents and symbolic interpretation of the painted scenes to answer specific questions and “take” the visitor close to the related paintings

A case of unexplained dyspnoea: When lung function testing matters!

Diverse methods are available for assessment of the respiratory muscles; the technique used should be tailored to the question posed. http://ow.ly/ChbX30m91bt

Thoracoabdominal asynchrony contributes to exercise limitation in mild asthmatic subjects

This study aimed to better understand how subjects with stable asthma and without exercise-induced bronchoconstriction respond to mild exercise. Breathing pattern, chest wall compartmental and operational volumes, and thoracoabdominal asynchrony were assessed in 11 stable asthmatic subjects and 10 healthy subjects at rest and during exercise in a cycle-ergometer through optoelectronic plethysmography. Dyspnea and sensation of leg effort were assessed through Borg scale. During exercise, with similar minute ventilation, a significant lower chest wall tidal volume (p = 0.003) as well as a higher respiratory rate (p < 0.05) and rapid shallow breathing (p < 0.05) were observed in asthmatic when compared to healthy subjects. Asthmatic subjects exhibited a significantly lower inspiratory (p < 0.05) and expiratory times (p < 0.05). Intergroup analysis found a significant higher end-expiratory chest wall volume in asthmatic subjects, mainly due to a significant increase in volume of the pulmonary ribcage (RCp; 170 ml, p = 0.002), indicating dynamic hyperinflation (DH). Dyspnea and sensation of leg effort were both significantly greater (p < 0.0001) in asthmatic when compared to healthy subjects. In addition to a higher thoracoabdominal asynchrony found between RCp and abdominal (AB) (p < 0.005) compartments in asthmatic subjects, post-inspiratory action of the inspiratory ribcage and diaphragm muscles were observed through the higher expiratory paradox time of both RCp (p < 0.0001) and AB (p = 0.0002), respectively. Our data suggest that a different breathing pattern is adopted by asthmatic subjects without exercise-induced bronchoconstriction during mild exercise and that this feature, associated with DH and thoracoabdominal asynchrony, contributes significantly to exercise limitation

Diferencias relacionadas con el sexo en pacientes con IAMCEST: análisis por puntuación de propensión

Supplementary data associated with this article can be found in the online version available at https://doi.org/ 10.24875/RECICE.M19000061.[EN] Introduction and objectives: Female sex is believed to be a significant risk factor for mortality among patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary interventions (pPCI). Methods: We collected data on all consecutive STEMI patients treated with pPCI within 12 hours and compared the males vs the females. The primary endpoint was long-term mortality one month after hospital discharge. The secondary endpoint was 30-days mortality. Results: From March 2006 to December 2016, 1981 patients underwent pPCI at our hospital, 484 (24.4%) were females. Compared with men, women were older (mean age 71.3 ± 11.6 vs 62.9 ± 11.8 years, P < .001), less smokers (26.7% vs 72.7%; P < .001), more diabetic (28.0% vs 22.3%; P < .002), more hypertensive (69.6% vs 61.3%; P < .001), presented more often with shock at baseline (13.2% vs 9.0%; P = .006), had longer symptoms-to-balloon time frames (5.36 ± 3.97 vs 4.47 ± 3.67 hours; P < .001). Also, women were less likely to receive glycoprotein IIb-IIIa inhibitors (59.5% vs 71.4%; P < .001) and stents (79.5% vs 86.6%; P = .01). During the 30-day and long-term follow-up (mean 4.9 ± 3.2 years) the female sex was associated with a higher mortality rate (8.9% vs 4.0%, P < .001 and 23.8% vs 18.4%, P = .01, respectively). After propensity score matching, 379 men and 379 women were selected. Female sex continued to be associated with a higher death rate at 30 days (9.5% vs 5.5%; P = .039) but not in the long term among survivors (25.6% vs 21.4%; P = .170). Conclusions: Compared to men, women with STEMI undergoing pPCI had higher 30-day mortality rates. However, among survivors, the long-term mortality rate was similar. Even if residual confounding cannot be ruled out, this difference in the outcomes may be partially explained by biological sex-related differences.[ES]Introducción y objetivos: El sexo femenino se considera un importante factor de riesgo de mortalidad en el infarto agudo de miocardio con elevación del segmento ST (IAMCEST) tratado con intervención coronaria percutánea primaria (ICPp). Métodos: Se analizó a todos los pacientes consecutivos con IAMCEST tratados con ICPp dentro de las primeras 12 horas, y se compararon varones y mujeres. El objetivo principal fue la mortalidad a largo plazo en los supervivientes después del primer mes del alta, y el objetivo secundario fue la mortalidad a los 30 días. Resultados: Desde marzo de 2006 hasta diciembre de 2016 se trató con ICPp 1.981 a pacientes, de los cuales 484 (24,4%) eran mujeres. En comparación con los varones, las mujeres tenían mayor edad (edad media 71,3 ± 11,6 frente a 62,9 ± 11,8 años, p < 0,001) y la frecuencia de fumadoras era más baja (26,7 frente a 72,7%; p < 0,001), mientras que era más alta la frecuencia de diabetes (28,0 frente a 22,3%; p < 0,002), hipertensión arterial (69.6 frente a 61,3%, p < 0,001) y shock al ingreso (13,2 frente a 9,0%; p = 0,006), y más largo el tiempo desde el comienzo de los síntomas hasta la intervención con balón (5,36 ± 3,97 frente a 4,47 ± 3,67 horas; p < 0,001). Además, la frecuencia de tratamiento con inhibidores de la glucoproteína IIb-IIIa (59,5 frente a 71,4%; p < 0,001) y stent (79,5 frente a 86,6%, p = 0,01) fue inferior. Tanto a los 30 días como a largo plazo (media 4,9 ± 3,2 años), el sexo femenino se asoció con una mortalidad más alta (8,9 frente a 4,0%, p < 0,001, y 23,8 frente a 18,4%, p = 0,01, respectivamente). Se seleccionaron 379 mujeres y 379 varones emparejados por puntuación de propensión. Se mantuvo la asociación entre sexo femenino y mayor mortalidad a los 30 días (9,5 frente a 5,5%; p = 0,039), pero no a largo plazo (25,6 frente a 21,4%; p = 0,170). Conclusiones: En comparación con los varones, las mujeres con IAMCEST tratadas con ICPp tuvieron mayor mortalidad a los 30 días. Sin embargo, entre los supervivientes, la mortalidad a largo plazo fue similar. Aunque no puede descartarse el efecto de variables residuales de confusión, las diferencias en el pronóstico podrían explicarse en parte por diferencias biológicas relacionadas con el sexo.S

Gender-related differences among patients with STEMI: a propensity score analysis

Se puede consultar material adicional a este artículo en su versión electrónica disponible en https://doi.org/10.24875/ RECIC.M19000072.[ES] Introducción y objetivos: El sexo femenino se considera un importante factor de riesgo de mortalidad en el infarto agudo de miocardio con elevación del segmento ST (IAMCEST) tratado con intervención coronaria percutánea primaria (ICPp). Métodos: Se analizó a todos los pacientes consecutivos con IAMCEST tratados con ICPp dentro de las primeras 12 horas, y se compararon varones y mujeres. El objetivo principal fue la mortalidad a largo plazo en los supervivientes después del primer mes del alta, y el objetivo secundario fue la mortalidad a los 30 días. Resultados: Desde marzo de 2006 hasta diciembre de 2016 se trató con ICPp a 1.981 pacientes, de los cuales 484 (24,4%) eran mujeres. En comparación con los varones, las mujeres tenían mayor edad (edad media 71,3 ± 11,6 frente a 62,9 ± 11,8 años, p < 0,001) y la frecuencia de fumadoras era más baja (26,7 frente a 72,7%; p < 0,001), mientras que era más alta la frecuencia de diabetes (28,0 frente a 22,3%; p < 0,002), hipertensión arterial (69.6 frente a 61,3%, p < 0,001) y shock al ingreso (13,2 frente a 9,0%; p = 0,006), y más largo el tiempo desde el comienzo de los síntomas hasta la intervención con balón (5,36 ± 3,97 fren- te a 4,47 ± 3,67 horas; p < 0,001). Además, la frecuencia de tratamiento con inhibidores de la glucoproteína IIb-IIIa (59,5 frente a 71,4%; p < 0,001) y stent (79,5 frente a 86,6%, p = 0,01) fue inferior. Tanto a los 30 días como a largo plazo (media 4,9 ± 3,2 años), el sexo femenino se asoció con una mortalidad más alta (8,9 frente a 4,0%, p < 0,001, y 23,8 frente a 18,4%, p = 0,01, res­pec­tivamente). Se seleccionaron 379 mujeres y 379 varones emparejados por puntuación de propensión. Se mantuvo la asociación entre sexo femenino y mayor mortalidad a los 30 días (9,5 frente a 5,5%; p = 0,039), pero no a largo plazo (25,6 frente a 21,4%; p = 0,170). Conclusiones: En comparación con los varones, las mujeres con IAMCEST tratadas con ICPp tuvieron mayor mortalidad a los 30 días. Sin embargo, entre los supervivientes, la mortalidad a largo plazo fue similar. Aunque no puede descartarse el efecto de variables residuales de confusión, las diferencias en el pronóstico podrían explicarse en parte por diferencias biológicas relacionadas con el sexo.[EN] Introduction and objectives: Female sex is believed to be a significant risk factor for mortality among patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary interventions (pPCI). Methods: We collected data on all consecutive STEMI patients treated with pPCI within 12 hours and compared the males vs the females. The primary endpoint was long-term mortality one month after hospital discharge. The secondary endpoint was 30-days mortality. Results: From March 2006 to December 2016, 1981 patients underwent pPCI at our hospital, 484 (24.4%) were females. Compared with men, women were older (mean age 71.3 ± 11.6 vs 62.9 ± 11.8 years, P < .001), less smokers (26.7% vs 72.7%; P < .001), more diabetic (28.0% vs 22.3%; P < .002), more hypertensive (69.6% vs 61.3%; P < .001), presented more often with shock at baseline (13.2% vs 9.0%; P = .006), had longer symptoms-to-balloon time frames (5.36 ± 3.97 vs 4.47 ± 3.67 hours; P < .001). Also, women were less likely to receive glycoprotein IIb-IIIa inhibitors (59.5% vs 71.4%; P < .001) and stents (79.5% vs 86.6%; P = .01). During the 30-day and long-term follow-up (mean 4.9 ± 3.2 years) the female sex was associated with a higher mortality rate (8.9% vs 4.0%, P < .001 and 23.8% vs 18.4%, P = .01, respectively). After propensity score matching, 379 men and 379 women were selected. Female sex continued to be associated with a higher death rate at 30 days (9.5% vs 5.5%; P = .039) but not in the long term among survivors (25.6% vs 21.4%; P = .170). Conclusions: Compared to men, women with STEMI undergoing pPCI had higher 30-day mortality rates. However, among survivors, the long-term mortality rate was similar. Even if residual confounding cannot be ruled out, this difference in the outcomes may be partially explained by biological sex-related differences.S

Impact of social determinants on antiretroviral therapy access and outcomes entering the era of universal treatment for people living with HIV in Italy

Background: Social determinants are known to be a driving force of health inequalities, even in high income countries. Aim of our study was to determine if these factors can limit antiretroviral therapy (ART) access, outcome and retention in care of people living with HIV (PLHIV) in Italy. Methods: All ART naïve HIV+ patients (pts) of Italian nationality enrolled in the ICONA Cohort from 2002 to 2016 were included. The association of socio-demographic characteristics (age, sex, risk factor for HIV infection, educational level, occupational status and residency area) with time to: ART initiation (from the first positive anti-HIV test), ART regimen discontinuation, and first HIV-RNA &lt; 50 cp/mL, were evaluated by Cox regression analysis, Kaplan Meier method and log-rank test. Results: A total of 8023 HIV+ pts (82% males, median age at first pos anti-HIV test 36 years, IQR: 29-44) were included: 6214 (77.5%) started ART during the study period. Women, people who inject drugs (PWID) and residents in Southern Italy presented the lowest levels of education and the highest rate of unemployment compared to other groups. Females, pts aged &gt; 50 yrs., unemployed vs employed, and people with lower educational levels presented the lowest CD4 count at ART initiation compared to other groups. The overall median time to ART initiation was 0.6 years (yrs) (IQR 0.1-3.7), with a significant decrease over time [2002-2006 = 3.3 yrs. (0.2-9.4); 2007-2011 = 1.0 yrs. (0.1-3.9); 2012-2016 = 0.2 yrs. (0.1-2.1), p &lt; 0.001]. By multivariate analysis, females (p &lt; 0.01) and PWID (p &lt; 0.001), presented a longer time to ART initiation, while older people (p &lt; 0.001), people with higher educational levels (p &lt; 0.001), unemployed (p = 0.02) and students (p &lt; 0.001) were more likely to initiate ART. Moreover, PWID, unemployed vs stable employed, and pts. with lower educational levels showed a lower 1-year probability of achieving HIV-RNA suppression, while females, older patients, men who have sex with men (MSM), unemployed had higher 1-year risk of first-line ART discontinuation. Conclusions: Despite median time to ART start decreased from 2002 to 2016, socio-demographic factors still contribute to disparities in ART initiation, outcome and durability

Rib Cage Deformities Alter Respiratory Muscle Action and Chest Wall Function in Patients with Severe Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is an inherited connective tissue disorder characterized by bone fragility, multiple fractures and significant chest wall deformities. Cardiopulmonary insufficiency is the leading cause of death in these patients.Seven patients with severe OI type III, 15 with moderate OI type IV and 26 healthy subjects were studied. In addition to standard spirometry, rib cage geometry, breathing pattern and regional chest wall volume changes at rest in seated and supine position were assessed by opto-electronic plethysmography to investigate if structural modifications of the rib cage in OI have consequences on ventilatory pattern. One-way or two-way analysis of variance was performed to compare the results between the three groups and the two postures. compared to predicted values, on condition that updated reference equations are considered. In both positions, ventilation was lower in OI patients than control because of lower tidal volume (p<0.01). In contrast to OI type IV patients, whose chest wall geometry and function was normal, OI type III patients were characterized by reduced (p<0.01) angle at the sternum (pectus carinatum), paradoxical inspiratory inward motion of the pulmonary rib cage, significant thoraco-abdominal asynchronies and rib cage distortions in supine position (p<0.001).In conclusion, the restrictive respiratory pattern of Osteogenesis Imperfecta is closely related to the severity of the disease and to the sternal deformities. Pectus carinatum characterizes OI type III patients and alters respiratory muscles coordination, leading to chest wall and rib cage distortions and an inefficient ventilator pattern. OI type IV is characterized by lower alterations in the respiratory function. These findings suggest that functional assessment and treatment of OI should be differentiated in these two forms of the disease