Rethinking Tako-tsubo Cardiomyopathy: The Contribution of Myocardial Pathology and Molecular Imaging.

BACKGROUND: Despite substantial research, the mechanisms behind stress Tako-tsubo cardiomyopathy (TTC) remain rather elusive. OBJECTIVE: The purpose of this paper was to provide a detailed review of the mainstream factors underlying the pathophysiology of TTC, highlighting the novel contributions of molecular pathology and in-vivo molecular imaging. METHODS: A careful literature review selected all papers discussing TTC, specifically those providing novel insights from myocardial pathology and cardiac molecular imaging. RESULTS: Results concerning myocardial pathology, defect extension, sites and relationships between functional parameters underline the existence of a causal relationship between a determinant (e.g., the release of catecholamines induced by stress) and an outcome for TTC, which is not limited to a reversible contractile cardiomyopathy, but it includes reversible changes in myocardial perfusion and a long-lasting residual deficit in sympathetic function. Besides, they reinforce the hypothesis that sympathetic nerves may exert a complex control on cardiac contractile function, which is likely to be direct or indirect through metabolism and microvascular perfusion changes during anaerobic and aerobic conditions. CONCLUSION: TTC is characterized by acute transient left ventricular systolic dysfunction, which can be challenging to distinguish from myocardial infarction at presentation. Catecholamineinduced myocardial injury is the most established theory, but other factors, including myocardial metabolism and perfusion, should be considered of utmost importance. Each effort to clarify the numerous pathways and emerging abnormalities may provide novel approaches to treat the acute episode, avoid recurrences, and prevent major adverse cardiovascular events.

Object stiffness recognition and vibratory feedback without ad-hoc sensing on the Hannes prosthesis: A machine learning approach.

Introduction: In recent years, hand prostheses achieved relevant improvements in term of both motor and functional recovery. However, the rate of devices abandonment, also due to their poor embodiment, is still high. The embodiment defines the integration of an external object - in this case a prosthetic device - into the body scheme of an individual. One of the limiting factors causing lack of embodiment is the absence of a direct interaction between user and environment. Many studies focused on the extraction of tactile information via custom electronic skin technologies coupled with dedicated haptic feedback, though increasing the complexity of the prosthetic system. Contrary wise, this paper stems from the authors' preliminary works on multi-body prosthetic hand modeling and the identification of possible intrinsic information to assess object stiffness during interaction. Methods: Based on these initial findings, this work presents the design, implementation and clinical validation of a novel real-time stiffness detection strategy, without ad-hoc sensing, based on a Non-linear Logistic Regression (NLR) classifier. This exploits the minimum grasp information available from an under-sensorized and under-actuated myoelectric prosthetic hand, Hannes. The NLR algorithm takes as input motor-side current, encoder position, and reference position of the hand and provides as output a classification of the grasped object (no-object, rigid object, and soft object). This information is then transmitted to the user via vibratory feedback to close the loop between user control and prosthesis interaction. This implementation was validated through a user study conducted both on able bodied subjects and amputees. Results: The classifier achieved excellent performance in terms of F1Score (94.93%). Further, the able-bodied subjects and amputees were able to successfully detect the objects' stiffness with a F1Score of 94.08% and 86.41%, respectively, by using our proposed feedback strategy. This strategy allowed amputees to quickly recognize the objects' stiffness (response time of 2.82 s), indicating high intuitiveness, and it was overall appreciated as demonstrated by the questionnaire. Furthermore, an embodiment improvement was also obtained as highlighted by the proprioceptive drift toward the prosthesis (0.7 cm).

COVID-19 Pandemic and Remote Consultations in Children: A Bibliometric Analysis.

Telemedicine is becoming a standard method of consultation, and the COVID-19 pandemic has increased its need. Telemedicine is suitable for non-communicable diseases (NCDs) in the pediatric population, as these are chronic conditions that affect many children worldwide. The aim of this study was to analyze the bibliometric parameters of publications on the use of telemedicine for the most common NCDs in children before and after the COVID-19 pandemic. Following the electronic search, 585 records were selected. "Metabolic diseases" was the most frequent topic before and after the pandemic, accounting for 34.76% in 2017-2019 and 33.97% in 2020-2022. The average IF of the journals from which records were retrieved was 5.46 ± 4.62 before and 4.58 ± 2.82 after the pandemic, with no significant variation. The number of citations per reference averaged 14.71 ± 17.16 in 2017-2019 (95% CI: 12.07; 17.36) and 5.54 ± 13.71 in 2020-2022 (95% CI: 4.23; 6.86). Asthma, metabolic diseases, and neurodevelopmental disorders were the most explored topics. A relevant finding concerns the increasing number of observational studies after the pandemic, with a reduction of the interventional studies. The latter type of study should be recommended as it can increase the evaluation of new strategies for the management of NCDs.

Neuropsychiatric or Behavioral and Psychological Symptoms of Dementia (BPSD): Focus on Prevalence and Natural History in Alzheimer's Disease and Frontotemporal Dementia.

Neuropsychiatric or behavioral and psychological symptoms of dementia (BPSD) represent a heterogeneous group of non-cognitive symptoms that are virtually present in all patients during the course of their disease. The aim of this study is to examine the prevalence and natural history of BPSD in a large cohort of patients with behavioral variant of frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) in three stages: (i) pre-T0 (before the onset of the disease); (ii) T0 or manifested disease (from the onset to 5 years); (iii) T1 or advanced (from 5 years onwards). Six hundred seventy-four clinical records of patients with bvFTD and 1925 with AD, from 2006 to 2018, were studied. Symptoms have been extracted from Neuropsychiatric Inventory (NPI) and from a checklist of BPSD for all periods observed. In our population, BPSD affect up to 90% of all dementia subjects over the course of their illness. BPSD profiles of the two dementia groups were similar but not identical. The most represented symptoms were apathy, irritability/affective lability, and agitation/aggression. Considering the order of appearance of neuropsychiatric symptoms in AD and bvFTD, mood disorders (depression, anxiety) come first than the other BPSD, with the same prevalence. This means that they could be an important "red flag" in detection of dementia. With the increase of disease severity, aberrant motor behavior and wandering were significantly more present in both groups. Differences between BPSD in AD and bvFTD resulted only in prevalence: Systematically, in bvFTD, all the symptoms were more represented than in AD, except for hallucinations, depression, anxiety, and irritability. Given their high frequency and impact on management and overall health care resources, BPSD should not be underestimated and considered as an additional important diagnostic and therapeutic target both in patients with AD and bvFTD.

COVID-19: persistence of symptoms and lung alterations after 3-6 months from hospital discharge.

PURPOSE: Few data are currently available on persistent symptoms and late organ damage in patients who have suffered from COVID-19. This prospective study aimed to evaluate the results of a follow-up program for patients discharged from a nonintensive COVID-19 ward. METHODS: 3-6 months after hospital discharge, 59 of 105 COVID-19 patients (31 males, aged 68.2 ± 12.8 years) were recruited in the study. Forty-six patients were excluded because of nontraceability, refusal, or inability to provide informed consent. The follow-up consisted of anamnesis (including a structured questionnaire), physical examination, blood tests, ECG, lower limb compression venous ultrasound (US), thoracic US, and spirometry with diffusion lung capacity for carbon monoxide (DLCO). RESULTS: 22% of patients reported no residual symptoms, 28.8% 1 or 2 symptoms and 49.2% 3 or more symptoms. The most frequently symptoms were fatigue, exertional dyspnea, insomnia, and anxiety. Among the inflammatory and coagulation parameters, only the median value of fibrinogen was slightly above normal. A deep vein thrombosis was detected in 1 patient (1.7%). Thoracic US detected mild pulmonary changes in 15 patients (25.4%), 10 of which reported exertional dyspnea. DLCO was mildly or moderately reduced in 19 patients (37.2%), 13 of which complained of exertional dyspnea. CONCLUSION: These results highlight that a substantial percentage of COVID-19 patients (77.8%) continue to complain of symptoms 3-6 months after hospital discharge. Exertional dyspnea was significantly associated with the persistence of lung US abnormalities and diffusing capacity alterations. Extended follow-up is required to assess the long-term evolution of postacute sequelae of COVID-19.

Evaluation of E-Health Applications for Paediatric Patients with Refractory Epilepsy and Maintained on Ketogenic Diet.

E-health technologies improve healthcare quality and disease management. The aim of this study was to develop a ketogenic diet management app as well as a website about this dietary treatment and to evaluate the benefits of giving caregivers access to various web materials designed for paediatric patients with refractory epilepsy. Forty families participated in the questionnaire survey, from January 2016 to March 2016. All caregivers were exposed to paper-based materials about the ketogenic diet, whereas only 22 received the app, called KetApp, and videos produced by dieticians. Caregivers with free access to web materials were more satisfied than the others with the informative material provided by the centre (p ≤ 0.001, Mann-Whitney test). Indeed, they showed a better attitude towards treatment, and they became more aware of dietary management in comparison to the control group (p ≤ 0.001). Moreover, caregivers provided with web materials were stimulated to pursue the treatment (p = 0.002) and to introduce it to their children and other people (p = 0.001). Additionally, caregivers supplied with web materials were more willing to help other families in choosing the ketogenic diet (p = 0.004). Overall, these findings indicate that web materials are beneficial for caregivers of paediatric patients with refractory epilepsy in our centres. Thus, the use of e-health applications could be a promising tool in the daily aspects of ketogenic diet management, and it is especially of value in the attempt to start or maintain the diet during the ongoing COVID-19 pandemic crisis.

Impacts of subclinical hypocalcemia on physiological, metabolic, and productive responses of Holstein × Gir dairy cows.

This study compared physiological and productive parameters in ¾ Holstein × » Gir dairy cows diagnosed or not with subclinical hypocalcemia (SCH) during early lactation. Nonlactating, multiparous cows (n = 32) were enrolled in this experiment 21 d prior to expected date of calving. Cows were maintained in a single pen with ad libitum access to corn silage before calving and received a limit-fed prepartum concentrate. Cow body weight (BW) and body condition score (BCS) were recorded weekly, and blood samples were collected on days -21, -14, -9, -6, and -3 relative to expected calving. After calving (day 0), cows were managed in a single pen with ad libitum access to a total mixed ration, and were milked twice daily. Cow BW and BCS were recorded upon calving and then weekly. Milk production was recorded daily and milk samples collected weekly until 30 d in milk (DIM). Blood was collected during the first 5 DIM, and at 6, 9, 16, 23, and 30 DIM. Cows were classified with SCH when mean total serum Ca during the first 5 DIM was ≤2.125 mmol/L. Cows diagnosed with SCH (n = 11) had less (P ≤ 0.04) mean BCS (2.85 vs. 3.07; SEM = 0.07) and less concentrations of serum insulin (0.396 vs. 0.738 ppmol/L; SEM = 0.115) and insulin-like growth factor I (35.9 vs. 57.9 ng/mL; SEM = 4.2), and these outcomes were noted since 21 d prior to expected calving. Cows diagnosed with SCH had greater (P < 0.01) serum concentrations of cortisol at calving (30.2 vs. 22.4 ng/mL; SEM = 2.0), serum haptoglobin at 3 and 6 DIM (0.453 vs. 0.280 mg/mL on day 3 and 0.352 vs. 0.142 mg/mL on day 6; SEM = 0.046), and tended (P = 0.09) to have greater mean concentrations of nonesterified fatty acids from calving to 30 DIM (0.368 vs. 0.304 µEq/L; SEM = 0.026). No differences were detected (P ≥ 0.41) for cow BW and milk production. Cows diagnosed with SCH had less (P = 0.05) mean concentrations of milk total solids (13.2 vs. 13.8 %; SEM = 0.21), tended to have less (P ≤ 0.10) mean concentrations of milk fat (4.34 vs. 4.81 %; SEM = 0.20), protein (3.31 vs. 3.45 %; SEM = 0.05), and lactose (4.45 vs. 4.55 %; SEM = 0.04), and had greater (P = 0.02) milk somatic cell count during the initial 14 DIM (504 vs. 140 cells/µL; SEM = 90). Collectively, Holstein × Gir cows diagnosed with SCH upon calving had altered periparturient physiological parameters denoting reduced energy nutritional, increased milk somatic cell count, and less concentration of milk components during early lactation compared with normocalcemic cows.

Multiple epitope presentation and surface density control enabled by chemoselective immobilization lead to enhanced performance in IgE-binding fingerprinting on peptide microarrays.

Multiple ligand presentation is a powerful strategy to enhance the affinity of a probe for its corresponding target. A promising application of this concept lies in the analytical field, where surface immobilized probes interact with their corresponding targets in the context of complex biological samples. Here we investigate the effect of multiple epitope presentation (MEP) in the challenging context of IgE-detection in serum samples using peptide microarrays, and evaluate the influence of probes surface density on the assay results. Using the milk allergen alpha-lactalbumin as a model, we have synthesized three immunoreactive epitope sequences in a linear, branched and tandem form and exploited a chemoselective click strategy (CuAAC) for their immobilization on the surface of two biosensors, a microarray and an SPR chip both modified with the same clickable polymeric coating. We first demonstrated that a fine tuning of the surface peptide density plays a crucial role to fully exploit the potential of oriented and multiple peptide display. We then compared the three multiple epitope presentations in a microarray assay using sera samples from milk allergic patients, confirming that a multiple presentation, in particular that of the tandem construct, allows for a more efficient characterization of IgE-binding fingerprints at a statistically significant level. To gain insights on the binding parameters that characterize antibody/epitopes affinity, we selected the most reactive epitope of the series (LAC1) and performed a Surface Plasmon Resonance Imaging (SPRi) analysis comparing different epitope architectures (linear versus branched versus tandem). We demonstrated that the tandem peptide provides an approximately twofold increased binding capacity with respect to the linear and branched peptides, that could be attributed to a lower rate of dissociation (Kd).

Screening Complex Biological Samples with Peptide Microarrays: The Favorable Impact of Probe Orientation via Chemoselective Immobilization Strategies on Clickable Polymeric Coatings.

The generation of robust analytical data using microarray platforms strictly relies on optimal ligand-target interaction at the sensor surface, which, in turn, is inherently bound to the correct immobilization scheme of the interrogated bioprobes. In the present work, we performed a rigorous comparative analysis of the impact of peptide ligands immobilization strategy in the screening of Burkholderia cepacia complex (BCC) infections in patients affected by cystic fibrosis (CF). We generated arrays of previously validated Burkholderia derived peptide probes that were selectively oriented on polymeric coatings by means of different click-type reactions including thiol maleimide, copper-catalyzed azide-alkyne cycloaddition (CuAAC), and strain-promoted azide-alkyne cycloaddition (SPAAC). We compared immobilization efficiency among the different chemoselective reactions, and we evaluated diagnostic performances at a statistically significant level, also in contrast to random immobilization strategies. Our findings clearly support the favorable role of correct bioprobe orientation in discriminating seronegative from infected individuals and, in the last analysis, in generating more-reliable and more-reproducible data. Spacing biomolecules from the sensor surface by means of small hydrophilic linkers also positively affects the analytical performance and leads to increased statistical significance of data. Overall, all of the click immobilization strategies that were considered displayed a good efficiency. Interestingly, SPAAC-mediated conjugation using DBCO cyclooctyne for some peptides resulted in sequence-dependent autofluorescence in the Cy5 emission range wavelength, which could be circumvented by using a different fluorescence detection channel. On the basis of our results, we critically discuss the immobilization parameters that need to be carefully considered for peptide ligand immobilization purposes.

Thoraco-abdominal motion/displacement does not affect dyspnea following exercise training in COPD patients.

PURPOSE: The interrelations among chest wall kinematics (displacement and configuration), ventilatory profile and dyspnea relief following cycle exercise training (EXT) have not been systematically evaluated in hyperinflated chronic obstructive pulmonary disease (COPD) patients. We hypothesize that a decrease in ventilation affects dyspnea relief, regardless of the changes in chest wall kinematics. METHODS: Fourteen patients were studied before and after 24-session exercise training program. We evaluated the volumes of chest wall and its compartments (rib cage, and abdomen) using optoelectronic plethysmography. RESULTS: At iso-time EXT (i) reduced ventilation, respiratory frequency and dyspnea (by Borg scale), mildly improved rib cage configuration, but left operational volumes unchanged; (ii) Borg was much smaller for any comparable inspiratory reserve volume (IRVcw), and a decrease in IRVcw was tolerated much better for any given Borg. CONCLUSIONS: Regardless of the changes in chest wall kinematics, a decrease in ventilation attenuates dyspnea following EXT.

Tidal volume inflection and its sensory consequences during exercise in patients with stable asthma.

Sixteen patients with stable asthma performed a symptom-limited constant work-rate CWR cycle exercise during which breathing pattern, operating lung volumes, dyspnea intensity and its qualitative descriptors were measured. An inflection in the relation between tidal volume (V(T)) and ventilation (V˙(E)) was observed in each subject. The sense of "work/effort" was the dominant dyspnea descriptor selected up to the V(T)/V˙(E) inflection, whereas after it dyspnea intensity and the selection frequency of "unsatisfied inspiration" rose steeply in 37.5% of subjects in whom inspiratory reserve volume (IRV) had decreased to a critical level of 0.6L at the V(T) inflection point. In contrast, dyspnea increased linearly with exercise time and V˙(E), and "work/effort" was the dominant descriptor selected throughout exercise in 62.5% of subjects in whom the V(T)/V˙(E) inflection occurred at a preserved IRV. The V(T) inflection during exercise in patients with stable asthma marked a mechanical event with important sensory consequences only when it occurred at a critical reduced IRV.

Obstructive sleep apnea (OSA) does not affect ventilatory and perceptual responses to exercise in morbidly obese subjects.

We have tested the hypothesis that high mass loading effects and obstructive sleep apnea (OSA) constrain the ventilatory response to exercise in morbidly obese subjects as compared to their counterparts without OSA. Fifteen obese patients with (8) and without OSA and 12 lean healthy subjects performed incremental cycle exercise. The functional evaluation included ventilation, oxygen uptake, carbon dioxide production, end-expiratory-lung-volumes (EELV), inspiratory capacity, heart rate, dyspnea and leg effort (by a modified Borg scale). Changes in ventilation and dyspnea per unit changes in work rate and metabolic variables were similar in the three groups. Breathing pattern and heart rate increased from rest to peak exercise similarly in the three groups. Leg effort was the prevailing symptom for stopping exercise in most subjects. In conclusion, OSA does not limit exercise capacity in morbidly obese subjects. Ventilation contributes to exertional dyspnea similarly as in lean subjects and in obese patients regardless of OSA.

Dyspnea, chest wall hyperinflation, and rib cage distortion in exercising patients with chronic obstructive pulmonary disease.

PURPOSE: Whether dyspnea, chest wall dynamic hyperinflation, and abnormalities of rib cage motion are interrelated phenomena has not been systematically evaluated in patients with chronic obstructive pulmonary disease (COPD). Our hypothesis that they are not interrelated was based on the following observations: (i) externally imposed expiratory flow limitation is associated with no rib cage distortion during strenuous incremental exercise, with indexes of hyperinflation not being correlated with dyspnea, and (ii) end-expiratory chest wall volume may either increase or decrease during exercise in patients with COPD, with those who hyperinflate being as breathless as those who do not. METHODS: Sixteen patients breathed either room air or 50% supplemental O2 at 75% of peak exercise in randomized order. We evaluated the volume of chest wall (V(cw)) and its compartments: the upper rib cage (V(rcp)), lower rib cage (V(rca)), and abdomen (V(ab)) using optoelectronic plethysmography; rib cage distortion was assessed by measuring the phase angle shift between V(rcp) and V(rca). RESULTS: Ten patients increased end-expiratory V(cw) (V(cw,ee)) on air. In seven hyperinflators and three non-hyperinflators, the lower rib cage paradoxed inward during inspiration with a phase angle of 63.4° ± 30.7° compared with a normal phase angle of 16.1° ± 2.3° recorded in patients without rib cage distortion. Dyspnea (by Borg scale) averaged 8.2 and 9 at the end of exercise on air in patients with and without rib cage distortion, respectively. At iso-time during exercise with oxygen, decreased dyspnea was associated with a decrease in ventilation regardless of whether patients distorted the rib cage, dynamically hyperinflated, or deflated the chest wall. CONCLUSIONS: Dyspnea, chest wall dynamic hyperinflation, and rib cage distortion are not interrelated phenomena.

Chest wall kinematics and breathlessness during unsupported arm exercise in COPD patients.

We hypothesised that chest wall displacement inappropriate to increased ventilation contributes to dyspnoea more than dynamic hyperinflation or dyssynchronous breathing during unsupported arm exercise (UAE) in COPD patients. We used optoelectronic plethysmography to evaluate operational volumes of chest wall compartments, the upper rib cage, lower rib cage and abdomen, at 80% of peak incremental exercise in 13 patients. The phase shift between the volumes of upper and lower rib cage (RC) was taken as an index of RC distortion. With UAE, no chest wall dynamic hyperinflation was found; sometimes the lower RC paradoxed inward while in other patients it was the upper RC. Phase shift did not correlate with dyspnoea (by Borg scale) at any time, and chest wall displacement was in proportion to increased ventilation. In conclusions neither chest wall dynamic hyperinflation nor dyssynchronous breathing per se were major contributors to dyspnoea. Unlike our prediction, chest wall expansion and ventilation were adequately coupled with each other.

Impact of a rehabilitation program on dyspnea intensity and quality in patients with chronic obstructive pulmonary disease.

BACKGROUND: It has yet to be determined whether the language of dyspnea responds to pulmonary rehabilitation programs (PRP). OBJECTIVE: We tested the hypothesis that PRP affect both the intensity and quality of exercise-induced dyspnea in patients with chronic obstructive pulmonary disease (COPD). METHODS: We studied 49 patients equipped with a portable telemetric spiroergometry device during the 6-min walking test before and 4 weeks after PRP. In a first screening visit, appropriate verbal descriptors of dyspnea were chosen that patients were familiar with during daily living activities. Tidal volume, respiratory frequency, inspiratory capacity, inspiratory reserve volume (IRV) and dyspnea intensity were evaluated by a modified Borg scale every minute during the test. RESULTS: Qualitative descriptors of dyspnea were defined by three different sets of cluster descriptors (a-c) at the end of the exercise test, before and after PRP: a - work/effort (W/E); b - inspiratory difficulty (ID) and chest tightness (CT), and c - W/E, ID and/or CT. The three language subgroups exhibited similar lung function at baseline, and similar rating of dyspnea and ventilatory changes during exercise. The rehabilitation program shifted the Borg-IRV relationship (less Borg at any given IRV) towards the right without modifying the set of descriptors in most patients. CONCLUSIONS: Rehabilitation programs allowed patients to tolerate a greater amount of restrictive dynamic ventilatory defect by modifying the intensity, but not necessarily the quality of dyspnea.

Effect of limb muscle fatigue on perception of respiratory effort in healthy subjects.

The role of nonrespiratory peripheral afferents in dyspnea perception has not been fully elucidated yet. Our hypothesis is that fatigue-induced activation of limb muscle metaboreceptors served by group IV fine afferent fibers may impact on respiratory effort perception. We studied 12 healthy subjects breathing against progressive inspiratory resistive loads (10, 18, 30, 40, and 90 cmH(2)O x l(-1) x s) before and after inducing low-frequency fatigue of quadriceps muscle by repeating sustained contractions at > or = 80% of maximal voluntary contraction. Subjects also underwent a sham protocol while performing two loaded breathing runs without muscle fatigue in between. During the loaded breathing, while subjects mimicked the quiet breathing pattern using a visual feedback, ventilation, tidal volume, respiratory frequency, pleural pressure swings, arterial oxygen saturation, end-tidal partial pressure of CO(2), and dyspnea by a Borg scale were recorded. Compared with prefatigue, limb muscle fatigue resulted in a higher increase in respiratory effort perception for any given ventilation, tidal volume, respiratory frequency, pleural pressure swings, end-tidal partial pressure of CO(2), and arterial oxygen saturation. No difference between the two runs was observed with the sham protocol. The present data support the hypothesis that fatigue of limb muscles increases respiratory effort perception associated with loaded breathing, likely by the activation of limb muscle metaboreceptors.

Do obstructive and restrictive lung diseases share common underlying mechanisms of breathlessness?

This review tries to answer two main questions: (i) What are the neurophysiological underpinnings of the most commonly selected cluster descriptors which define the qualitative dimension of dyspnea in patients? (ii) How do mechanical constraints affect dyspnea? (iii) Do obstructive and restrictive lung diseases share some common underlying mechanisms? Qualitative dimensions of dyspnea, which allude to increased respiratory work/effort breathing, reflect a harmonious coupling between increased respiratory motor output and lung volume displacement in healthy subjects. Descriptors that allude to unsatisfied inspiration are the dominant qualitative descriptors in patients with a variety of respiratory diseases. It is possible that sensory feedback from a multitude of mechanoreceptors throughout the respiratory system (in the muscle, chest wall, airways and lung parenchyma) collectively convey information to the consciousness that volume/flow or chest wall displacement is inadequate for the prevailing respiratory drive. The data would lend support to the idea that: (i) an altered afferent proprioceptive peripheral feedback signals that ventilatory response is inadequate to the prevailing motor drive, reflecting neuromechanical uncoupling (NMU), (ii) mechanical constraints on volume expansion (dynamic restriction) play a pivotal role in dyspnea causation in patients with a variety of either obstructive or restrictive respiratory disorders, and (iii) all of the physiological adaptations that optimize neuromechanical coupling in obstructive and restrictive disorders are seriously disrupted so that an NMU underpins cluster descriptors of dyspnea which are similar in obstructed and in restricted patients.

Airway hyperresponsiveness with chest strapping: A matter of heterogeneity or reduced lung volume?

Chest wall strapping has been recently shown to be associated with an increase in airway responsiveness to methacholine. To investigate whether this is the result of the decreased lung volume or an increased heterogeneity due to chest wall distortion, ten healthy volunteers underwent a methacholine challenge at control conditions and after selective strapping of the rib cage, the abdomen or the whole chest wall resulting in similar decrements of functional residual capacity and total lung capacity but causing different distribution of the bronchoconstrictor. Methacholine during strapping reduced forced expiratory flow, dynamic compliance, and reactance at 5Hz and increased pulmonary resistance and respiratory resistance at 5Hz that were significantly greater than at control and associated with a blunted bronchodilator effect of the deep breath. However, no significant differences were observed between selective and total chest wall strapping, suggesting that the major mechanism for increasing airway responsiveness with chest wall strapping is the breathing at low lung volume rather than regional heterogeneities.

The respiratory muscles in eucapnic obesity: their role in dyspnea.

Regular exercise appears to be one of the best predictors of successful weight maintenance. Although physical activity and exercise are important components in the prevention and treatment of obesity, many obese adults without coexisting disorders are unable to exercise due to dyspnea on exertion. As a result they may not participate in regular physical activity. Therefore exertional dyspnea in obese adults is also an obstacle to the prevention and treatment of obesity and coexisting comorbidities. The available data suggest that increased respiratory muscle force generation, and the concomitant increase in respiratory neural drive associated with increased ventilation are an important source of sensation of respiratory effort in obese subjects. Whether activity-related breathlessness is due to either abnormal respiratory mechanical factors (flow limitation and/or chest elastic loading) or the increased metabolic demand of locomotion in obesity, or both of these together, the available data indicate that intensity of dyspnea at any given ventilation and oxygen uptake does not increase in obese subjects as compared with normal weight control subjects. Does this mean that respiratory mechanical factors are unlikely to be contributory? Nonetheless, the component of metabolic cost of breathing may not be accounted for in the measured mechanical work of breathing because of the number of included complex variables. That a decrease in efficiency of the respiratory muscles during exercise contributes to dyspnea in hyperinflating obese subjects should not be disregarded.