Asthma is a prevalent inflammatory condition of the lower airways characterized byvariable and recurring symptoms, reversible airflow obstruction, and bronchialhyperresponsiveness (BHR). Symptomatically, these patients may demonstrate wheezing,breathlessness, chest tightness, and coughing. This disease is a substantial burden to a growingpopulation worldwide that currently exceeds 300 million individuals. This is a condition that isfrequently encountered, but often overlooked in the field of otolaryngology. In asthma, comorbidconditions are routinely present and contribute to respiratory symptoms, decreased quality of life,and poorer asthma control. It is associated with otolaryngic diseases of the upper airways includingallergic rhinitis (AR) and chronic rhinosinusitis (CRS). These conditions have been linkedepidemiologically and pathophysiologically. Presently, they are considered in the context of theunified airway theory, which describes the upper and lower airways as a single functional unit.Thus, it is important for otolaryngologists to understand asthma and its complex relationships tocomorbid diseases, in order to provide comprehensive care to these patients. In this article, wereview key elements necessary for understanding the evaluation and management of asthma andits interrelatedness to CRS.

Peripheral artery disease (PAD) is an atherosclerotic disease that impairs blood flow and muscle function in the lower limbs. A skeletal muscle myopathy characterized by mitochondrial dysfunction and oxidative damage is present in PAD; however, the underlying mechanisms are not well-established. We investigated the impact of chronic ischemia on skeletal muscle microcirculatory function and its association with leg skeletal muscle mitochondrial function and oxygen delivery and utilization capacity in PAD. Gastrocnemius samples and arterioles were harvested from patients with PAD (n=10) and age-matched controls (CON, n=11). Endothelial-dependent and independent vasodilation was assessed in response to flow (30μL∙min-1), acetylcholine, and sodium nitroprusside (SNP). Skeletal muscle mitochondrial respiration was quantified by high-resolution respirometry, and microvascular oxygen delivery and utilization capacity (TOI) was assessed by near-infrared spectroscopy. Vasodilation was attenuated in PAD (P<0.05) in response to acetylcholine (CON: 71.1±11.1%, PAD: 45.7±18.1%) and flow (CON: 46.6±20.1%, PAD: 29.3±10.5%) but not SNP (P=0.30). Complex I+II state 3 respiration (P<0.01) and TOI recovery rate were impaired in PAD (P<0.05). Both flow and acetylcholine-mediated vasodilation were positively associated with complex I+II state 3 respiration (r=0.5 and r=0.5, respectively, P<0.05). Flow-mediated vasodilation and complex I+II state 3 respiration were positively associated with TOI recovery rate (r=0.8 and r=0.7, respectively, P<0.05). These findings suggest that chronic ischemia attenuates skeletal muscle arteriole endothelial function, which may be a key mediator for mitochondrial and microcirculatory dysfunction in the PAD leg skeletal muscle. Targeting microvascular dysfunction may be an effective strategy to prevent and/or reverse disease progression in PAD.

Peripheral artery disease (PAD) is characterized by the development of atherosclerotic plaques in the lower-body conduit arteries. PAD is commonly accompanied by microvascular disease, which may result in poor wound healing, plantar ulcer development, and subsequent limb amputation. Understanding the mechanisms underlying the development of plantar ulcers is a critical step in the development of adequate treatment options for patients with PAD. Skin is classified into two major components: glabrous and non-glabrous. These skin types have unique microcirculation characteristics, making it important to differentiate between the two when investigating mechanisms for plantar ulcer development in PAD. There is evidence for a microcirculation compensatory mechanism in PAD. This is evident by the maintenance of basal microcirculation perfusion and capillary filling pressure despite a reduced pressure differential beyond an occlusion in non-critical limb ischemia PAD. The major mechanism for this compensatory system seems to be progressive vasodilation of the arterial network below an occlusion. Recently, heat therapies have emerged as novel treatment options for attenuating the progression of PAD. Heat therapies are capable of stimulating the cardiovascular system, which may lead to beneficial adaptations that may ultimately reduce fatigue during walking in PAD. Early work in this area has shown that full-body heating is capable of generating an acute cardiovascular response, similar to exercise, which has been suggested as the most efficient treatment modality and may generate adaptations with chronic exposure. Heat therapies may emerge as a conservative treatment option capable of attenuating the progression of PAD and ultimately impeding the development of plantar ulcers.

Alzheimer's disease (AD) is a progressive degenerative brain disease and the primary cause of dementia. At an early stage, AD is generally characterized by short-term memory impairment, owing to dysfunctions of the cortex and hippocampus. We previously reported that a combination of exercise and 40 Hz light flickering can protect against AD-related neuroinflammation, gamma oscillations, reduction in Aβ, and cognitive decline. Therefore, we sought to extend our previous findings to the 5-month-old 3xTg-AD mouse model to examine whether the same favorable effects occur in earlier stages of cognitive dysfunction. We investigated the effects of 12 weeks of exercise combined with 40-Hz light flickering on cognitive function by analyzing neuroinflammation, mitochondrial function, and neuroplasticity in the hippocampus in a 3xTg-AD mouse model. 5-month-old 3xTg-AD mice performed 12 weeks of exercise with 40-Hz light flickering administered independently and in combination. Spatial learning and memory, long-term memory, hippocampal Aβ, tau, neuroinflammation, pro-inflammatory cytokine expression, mitochondrial function, and neuroplasticity, were analyzed. Aβ and tau proteins levels were significantly reduced in the early stage of AD, resulting in protection against cognitive decline by reducing neuroinflammation and pro-inflammatory cytokines. Furthermore, mitochondrial function improved, apoptosis was reduced, and synapse-related protein expression increased. Overall, exercise with 40-Hz light flickering was significantly more effective than exercise or 40-Hz light flickering alone, and the improvement was comparable to the levels in the non-transgenic aged-match control group. Our results indicate a synergistic effect of exercise and 40-Hz light flickering on pathological improvements in the hippocampus during early AD associated cognitive impairment.