Effect of Test Interface on Respiratory Muscle Activity and Pulmonary Function During Respiratory Testing in Healthy Adults: A Pilot Study.

Purpose: The mouthpiece is the standard interface for spirometry tests. Although the use of a mouthpiece can be challenging for patients with orofacial weakness, maintaining a proper seal with a facemask can be an issue for healthy individuals during forceful efforts. We compared respiratory muscle activity and tests using a mouthpiece and facemask in healthy adults to investigate whether they can be used interchangeably. Methods: In this observational study, subjects (n=12) completed forced vital capacity, maximal respiratory pressure, and peak cough flow with a mouthpiece and facemask. Root mean square values of the genioglossus, diaphragm, scalene, and sternocleidomastoid were compared between conditions. Results: When switching from a mouthpiece to a facemask, significantly higher values were seen for peak cough flow (average bias= -54.36 L/min, p<0.05) and the difference seen with MEP and MIP were clinically significant (average bias: MEP=27.33, MIP=-5.2). Additionally, submental activity was significantly greater when MIP was conducted with a mouthpiece. No significant differences were seen in respiratory muscle activity during resting breathing or spirometry. Conclusion: There are clinically significant differences with cough and MEP tests and neck muscles are activated differently based on interface. Considering the small sample size, our findings suggest a facemask may be used to complete some PFTs.

Exploring inspiratory occlusion metrics to assess respiratory drive in patients under acute intermittent hypoxia.

Patients living with Amyotrophic Lateral Sclerosis (ALS) experience respiratory weakness and, eventually, failure due to inspiratory motor neuron degeneration. Routine pulmonary function tests (e.g., maximum inspiratory pressure (MIP)) are used to assess disease progression and ventilatory compromise. However, these tests are poor discriminators between respiratory drive and voluntary respiratory function at rest. To better understand ALS disease progression, we can look into compensatory strategies and how patients consciously react to the occlusion and the effort produced to meet the ventilatory challenge of the occlusion. This ventilatory challenge, especially beyond the P0.1 (200 ms and 300 ms), provides information regarding the patient's ability to recruit additional respiratory muscles as a compensatory strategy. Utilizing a standard P0.1 protocol to assess respiratory drive, we extend the occlusion time analysis to 200 ms and 300 ms (Detected Occlusion Response (DOR)) in order to capture compensatory respiratory mechanics. Furthermore, we followed an Acute Intermittent Hypoxia (AIH) protocol known to increase phrenic nerve discharge to evaluate the compensatory strategies. Inspiratory pressure, the rate of change in pressure, and pressure generation normalized to MIP were measured at 100 ms, 200 ms, and 300 ms after an occlusion. Airway occlusions were performed three times during the experiment (i.e., baseline, 30 and 60 minutes post-AIH). Results indicated that while AIH did not elicit change in the P0.1 or MIP, the DOR increased for ALS patients. These results support the expected therapeutic role of AIH and indicate the potential of the DOR as a metric to detect compensatory changes.

Acute intermittent hypoxia and respiratory muscle recruitment in people with amyotrophic lateral sclerosis: A preliminary study.

Respiratory failure is the main cause of death in amyotrophic lateral sclerosis (ALS). Since no effective treatments to preserve independent breathing are available, there is a critical need for new therapies to preserve or restore breathing ability. Since acute intermittent hypoxia (AIH) elicits spinal respiratory motor plasticity in rodent ALS models, and may restore breathing ability in people with ALS, we performed a proof-of-principle study to investigate this possibility in ALS patients. Quiet breathing, sniff nasal inspiratory pressure (SNIP) and maximal inspiratory pressure (MIP) were tested in 13 persons with ALS and 10 age-matched controls, before and 60 min post-AIH (15, 1 min episodes of 10% O2, 2 min normoxic intervals) or sham AIH (continuous normoxia). The root mean square (RMS) of the right and left diaphragm, 2nd parasternal, scalene and sternocleidomastoid muscles were monitored. A vector analysis was used to calculate summated vector magnitude (Mag) and similarity index (SI) of collective EMG activity during quiet breathing, SNIP and MIP maneuvers. AIH facilitated tidal volume and minute ventilation (treatment main effects: p < 0.05), and Mag (ie. collective respiratory muscle activity; p < 0.001) during quiet breathing in ALS and control subjects, but there was no effect on SI during quiet breathing. SNIP SI decreased in both groups post-AIH (p < 0.005), whereas Mag was unchanged (p = 0.09). No differences were observed in SNIP or MIP post AIH in either group. Discomfort was not reported during AIH by any subject, nor were adverse events observed. Thus, AIH may be a safe way to increase collective inspiratory muscle activity during quiet breathing in ALS patients, although a single AIH presentation was not sufficient to significantly increase peak inspiratory pressure generation. These preliminary results provide evidence that AIH may improve breathing function in people with ALS, and that future studies of prolonged, repetitive AIH protocols are warranted.

Quadriceps architecture in individuals with patellofemoral pain: A systematic review.

OBJECTIVES: To identify differences in architectural parameters (size, fiber/pennation angle, fiber length, and echogenicity) of the quadriceps muscle, as a whole or any individual part of it, using imaging techniques in individuals with patellofemoral pain (PFP) compared to contralateral, asymptomatic limb or separate control group. BACKGROUND: Quadriceps muscles imbalance and weakness were proposed as risk factors for developing PFP. Although the muscle architecture (size, pennation/fiber angle and fiber length) is highly associated with skeletal muscle strength, it is not clear whether atrophy or any changes in architectural parameters of the quadriceps are presented in the PFP patients. METHODS: Observational studies in which the total size of the quadriceps or individual parts of it were measured using imaging techniques in the PFP patients were included in this review. Electronic databases (PubMed, SCOPUS, PEDro, CINAHL, WOS, and EMBASE) were searched between January 1990 and December 2019 with no restriction of language. Study selection and data extraction and quality assessment were conducted by two independent reviewers. RESULTS: Five cross-sectional studies were eligible to include in this review. Three out of five included studies that assessed the total size of the quadriceps and reported no significant differences between the PFP and healthy control group. Two out of five of the studies assessed the total size of the quadriceps between the symptomatic and asymptomatic limb of the PFP patients and reported the statistical difference between limbs. Only one study measured the fiber angle of the VMO muscle at the patella. Controversial results were found between studies that assessed the size of individual parts of the quadriceps. CONCLUSION: Due to the controversial results of the included studies, this systematic review failed to draw a conclusion on the role of quadriceps atrophy in PFP pathology. The limitation in PFP literature considering pennation/fiber angle, echogenicity and fiber length of individual parts of the quadriceps muscle, rises the need for research that focuses on the biomechanical properties of the quadriceps in PFP patients.

Adenosine 2A receptor inhibition protects phrenic motor neurons from cell death induced by protein synthesis inhibition.

Respiratory motor neuron survival is critical for maintenance of adequate ventilation and airway clearance, preventing dependence to mechanical ventilation and respiratory tract infections. Phrenic motor neurons are highly vulnerable in rodent models of motor neuron disease versus accessory inspiratory motor pools (e.g. intercostals, scalenus). Thus, strategies that promote phrenic motor neuron survival when faced with disease and/or toxic insults are needed to help preserve breathing ability, airway defense and ventilator independence. Adenosine 2A receptors (A2A) are emerging as a potential target to promote neuroprotection, although their activation can have both beneficial and pathogenic effects. Since the role of A2A receptors in the phrenic motor neuron survival/death is not known, we tested the hypothesis that A2A receptor antagonism promotes phrenic motor neuron survival and preserves diaphragm function when faced with toxic, neurodegenerative insults that lead to phrenic motor neuron death. We utilized a novel neurotoxic model of respiratory motor neuron death recently developed in our laboratory: intrapleural injections of cholera toxin B subunit (CtB) conjugated to the ribosomal toxin, saporin (CtB-Saporin). We demonstrate that intrapleural CtB-Saporin causes: 1) profound phrenic motor neuron death (~5% survival); 2) ~7-fold increase in phrenic motor neuron A2A receptor expression prior to cell death; and 3) diaphragm muscle paralysis (inactive in most rats; ~7% residual diaphragm EMG amplitude during room air breathing). The A2A receptor antagonist istradefylline given after CtB-Saporin: 1) reduced phrenic motor neuron death (~20% survival) and 2) preserved diaphragm EMG activity (~46%). Thus, A2A receptors contribute to neurotoxic phrenic motor neuron death, an effect mitigated by A2A receptor antagonism.

The effect of Tai Chi exercises on postural stability and control in older patients with knee osteoarthritis.

A few studies have examined the effect of Tai Chi on balance in elder patients with knee osteoarthritis (OA). The aim of this study was to determine the balance measures in elder patients with knee OA after Tai Chi exercises. For this purpose 14 females and 6 males with knee OA were chosen. Area and mean velocity of the center of pressure movements (CoP) were measured by force plate in standing positions (on foam and rigid surfaces). The measurements of area and mean velocity of CoP were performed before and after 60 min of Tai Chi sessions (twice a week for 8 weeks). The results showed that the area of CoP in standing position on rigid surface was significantly decreased (P < 0.01) after Tai Chi exercises. Furthermore, the mean velocity of CoP was significantly decreased after Tai Chi exercises on both rigid and foam surfaces (P < 0.001). Our study also indicated that changes in surfaces (rigid and foam) would cause significant differences regarding the area of CoP in standing positions. However, similar findings were not found regarding the mean velocity of CoP. Considering the effects of Tai Chi on mean velocity of CoP, it might be concluded that motor control and postural stability improvements have occurred. Therefore, based on these results, Tai Chi exercises could be recommended for elder patients with knee OA as part of their rehabilitation and physical therapy protocols.

Autophagy, apoptosis, mitoptosis and necrosis: interdependence between those pathways and effects on cancer.

Cell death is a fundamental ingredient of life. Thus, not surprisingly more than one form of cell death exists. Several excellent reviews on various forms of cell death have already been published but manuscripts describing interconnection and interdependence between such processes are uncommon. Here, what follows is a brief introduction on all three classical forms of cell death, followed by a more detailed insight into the role of p53, the master regulator of apoptosis, and other forms of cell death. While discussing p53 and also the role of caspases in cell death forms, we offer insight into the interplay between autophagy and apoptosis, or necrosis, where autophagy may initially serve pro-survival functions. The review moves further to present some details about less researched forms of programmed cell death, namely necroptosis, necrosis and mitoptosis. These "mixed" forms of cell death allow us to highlight the interconnected nature of cell death forms, particularly apoptosis and necrosis. The interdependence between apoptosis, autophagy and necrosis, and their significance for cancer development and treatment are also analyzed in further parts of the review. In the concluding parts, the afore-mentioned issues will be put in perspective for the development of novel anti-cancer therapies.