Sex, gender and the pulmonary physiology of exercise

In this review, we detail how the pulmonary system's response to exercise is impacted by both sex and gender in healthy humans across the lifespan. First, the rationale for why sex and gender differences should be considered is explored, and then anatomical differences are highlighted, namely that females typically have smaller lungs and airways than males. Thereafter, we describe how these anatomical differences can impact functional aspects such as respiratory muscle energetics and activation, mechanical ventilatory constraints, diaphragm fatigue, and pulmonary gas exchange in healthy adults and children. Finally, we detail how gender can impact the pulmonary response to exercise.

Standardised 3D-CT Lung Volumes for Patients with Idiopathic Pulmonary Fibrosis

Background: The assessment of lung physiology via pulmonary function tests (PFTs) is essential for patients with idiopathic pulmonary fibrosis (IPF). However, PFTs require active participation, which can be challenging for patients with severe respiratory failure, such as during acute exacerbations (AE) of IPF. Recently advances enabled to re-construct of 3-dimensional computed-tomography (3D-CT) images. Methods: This is a retrospective multi-center cohort study. This study established a standardisation method and quantitative analysis of lung volume (LV) based on anthropometry using three-dimensional computed tomography (3D-CT) images. The standardised 3D-CT LV in patients with IPF at diagnosis (n=140) and during AE (cohort1; n=61 and cohort2; n=50) and those of controls (n=53) were measured. Results: The standardised 3D-CT LVs at IPF diagnosis were less than those of control patients, especially in the lower lung lobes. The standardised 3D-CT LVs were correlated with forced vital capacity (FVC) and validated using the modified Gender-Age-Physiology (GAP) index. The standardised 3D-CT LVs at IPF diagnosis were independently associated with prognosis. During AE, PFTs were difficult to perform, 3D-CT analyses revealed reduced lung capacity in both the upper and lower lobes compared to those obtained at diagnosis. Lower standardised 3D-CT LVs during AE were independently associated with worse outcomes in independent two cohorts. Particularly, volume loss in the upper lobe at AE had prognostic values.Conclusion: A novel image quantification method for assessing pulmonary physiology using standardised 3D-CT-derived LVs was developed. This method successfully predicts mortality in patients with IPF and AE of IPF, and may be a useful alternative to PFTs when PFTs cannot be performed.

Literature Review: Risk Factors for Lung Physiological Disorders Due to Exposure to Wood Dust

Introduction: The wood processing industry in Indonesia is experiencing very rapid development, so there are positive and negative impacts of this industry for the country. The positive impacts that occur such as increased economic growth while the negative impacts that occur include environmental pollution which directly impacts the health of workers. One of the bad effects experienced by workers working in the industrial sector is wood dust. Wood dust is an invisible object that can circulate through the air so that it can enter the body and cause disruption of lung function of workers. The purpose of this research to conduct research on the factors of lung physiology disorders caused by vulnerability to wood dust. Method: The method was used in this research is a literature review by reviewing 10 relevant articles. Results: The effects showed that the method used is the same, which is using cross sectional, and during the study the data collection tools used questionnaires with interviews. In line with the outcomes of the study, factors for pulmonary physiology are not only caused by dust levels that exceeded the threshold value (NAV), but there are several other factors, namely individual characteristics such as length of service, duration of exposure, smoking habits, and use of personal protective equipment (PPE). Moreover, several studies presented bivariate tests to find out the relationship between variables that are factors in the occurrence of pulmonary physiology. Conclusions: Of 10 studies most have performed a bivariate analysis, but just a few have analyzed all the factors causing pulmonary physiology. Keywords: literature review, pulmonary physiology, risk factor, wood dust

A Damaged-Informed Lung Ventilator Model for Ventilator Waveforms

Motivated by a desire to understand pulmonary physiology, scientists have developed physiological lung models of varying complexity. However, pathophysiology and interactions between human lungs and ventilators, e.g., ventilator-induced lung injury (VILI), present challenges for modeling efforts. This is because the real-world pressure and volume signals may be too complex for simple models to capture, and while complex models tend not to be estimable with clinical data, limiting clinical utility. To address this gap, in this manuscript we developed a new damaged-informed lung ventilator (DILV) model. This approach relies on mathematizing ventilator pressure and volume waveforms, including lung physiology, mechanical ventilation, and their interaction. The model begins with nominal waveforms and adds limited, clinically relevant, hypothesis-driven features to the waveform corresponding to pulmonary pathophysiology, patient-ventilator interaction, and ventilator settings. The DILV model parameters uniquely and reliably recapitulate these features while having enough flexibility to reproduce commonly observed variability in clinical (human) and laboratory (mouse) waveform data. We evaluate the proof-in-principle capabilities of our modeling approach by estimating 399 breaths collected for differently damaged lungs for tightly controlled measurements in mice and uncontrolled human intensive care unit data in the absence and presence of ventilator dyssynchrony. The cumulative value of mean squares error for the DILV model is, on average, ≈12 times less than the single compartment lung model for all the waveforms considered. Moreover, changes in the estimated parameters correctly correlate with known measures of lung physiology, including lung compliance as a baseline evaluation. Our long-term goal is to use the DILV model for clinical monitoring and research studies by providing high fidelity estimates of lung state and sources of VILI with an end goal of improving management of VILI and acute respiratory distress syndrome.

Going to Extremes of Lung Physiology–Deep Breath-Hold Diving

Breath-hold diving involves environmental challenges, such as water immersion, hydrostatic pressure, and asphyxia, that put the respiratory system under stress. While training and inherent individual factors may increase tolerance to these challenges, the limits of human respiratory physiology will be reached quickly during deep breath-hold dives. Nonetheless, world records in deep breath-hold diving of more than 214 m of seawater have considerably exceeded predictions from human physiology. Investigations of elite breath-hold divers and their achievements revised our understanding of possible physiological adaptations in humans and revealed techniques such as glossopharyngeal breathing as being essential to achieve extremes in breath-hold diving performance. These techniques allow elite athletes to increase total lung capacity and minimize residual volume, thereby reducing thoracic squeeze. However, the inability of human lungs to collapse early during descent enables respiratory gas exchange to continue at greater depths, forcing nitrogen (N2) out of the alveolar space to dissolve in body tissues. This will increase risk of N2 narcosis and decompression stress. Clinical cases of stroke-like syndromes after single deep breath-hold dives point to possible mechanisms of decompression stress, caused by N2 entering the vasculature upon ascent from these deep dives. Mechanisms of neurological injury and inert gas narcosis during deep breath-hold dives are still incompletely understood. This review addresses possible hypotheses and elucidates factors that may contribute to pathophysiology of deep freediving accidents. Awareness of the unique challenges to pulmonary physiology at depth is paramount to assess medical risks of deep breath-hold diving.

The Role of Pulmonary Surfactants in the Treatment of Acute Respiratory Distress Syndrome in COVID-19

Lung alveolar type-II (AT-II) cells produce pulmonary surfactant (PS), consisting of proteins and lipids. The lipids in PS are primarily responsible for reducing the air-fluid surface tension inside the alveoli of the lungs and to prevent atelectasis. The proteins are of two types: hydrophilic and hydrophobic. Hydrophilic surfactants are primarily responsible for opsonisation, thereby protecting the lungs from microbial and environmental contaminants. Hydrophobic surfactants are primarily responsible for respiratory function. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters the lungs through ACE-2 receptors on lungs and replicates in AT-II cells leading to the etiology of Coronavirus disease – 2019 (COVID-19). The SARS-CoV-2 virus damages the AT-II cells and results in decreased production of PS. The clinical symptoms of acute respiratory distress syndrome (ARDS) in COVID-19 patients are like those of neonatal respiratory distress syndrome (NRDS). The PS treatment is first-line treatment option for NRDS and found to be well tolerated in ARDS patients with inconclusive efficacy. Over the past 70°years, a lot of research is underway to produce natural/synthetic PS and developing systems for delivering PS directly to the lungs, in addition to finding the association between PS levels and respiratory illnesses. In the present COVID-19 pandemic situation, the scientific community all over the world is searching for the effective therapeutic options to improve the clinical outcomes. With a strong scientific and evidence-based background on role of PS in lung homeostasis and infection, few clinical trials were initiated to evaluate the functions of PS in COVID-19. Here, we connect the data on PS with reference to pulmonary physiology and infection with its possible therapeutic benefit in COVID-19 patients.

Effects of cigarette smoke exposure on pulmonary physiology, muscle strength and exercise capacity in a retrospective cohort with 30,000 subjects

Background The effects of long-term cigarette smoke exposure on pulmonary physiology and how those effects lead to reduced exercise capacity are not well established. Methods We retrospectively analyzed the spirometry, single-breath gas transfer (DLCO), peripheral muscle strength, and maximum exercise capacity data in patients referred to McMaster University Medical Centre for cardiopulmonary exercise testing between 2000 and 2012. Results 29,441 subjects underwent CPET and had a recorded smoking history [58% male, mean age 51.1 years (S.D.±19.6), BMI 27.4 kg/m2(±5.8)]. 7081 (24%) were current or former smokers and were divided into 4 categories by packs years (mean ±S.D.): <10 (5.8±3.3), 10–20 (17.1±2.9), 20–30 (27.1±2.8), 30–40 (37.3±2.8), and >40 (53.9±12.8). Patients with greater cigarette smoke exposure had lower expiratory flow rates (FEV1, FEF50, FEF75, PEFR), DLCO, and maximum power output (MPO) during exercise. There was no association between smoke exposure and muscle strength. Modeling MPO (kpm/min) output as a function of demographic and physiologic variables showed that the data are well explained by muscle strength (kg), FEV1 (L), and DLCO (mmHg/min/mL) in similar magnitude (MPO = 42.7*Quads0.34*FEV10.34 * DLCO0.43; r = 0.84). Conclusions Long-term cigarette smoke exposure is associated with small airway narrowing and impaired diffusion capacity but not with peripheral muscle weakness. The effects of smoking, age, and gender on maximum power output are mediated by reductions in FEV1, muscle strength and DLCO. Exercise capacity in smokers may benefit from therapies targeting all 3 variables.

Mucus, Microbiomes and Pulmonary Disease

The respiratory tract harbors a stable and diverse microbial population within an extracellular mucus layer. Mucus provides a formidable defense against infection and maintaining healthy mucus is essential to normal pulmonary physiology, promoting immune tolerance and facilitating a healthy, commensal lung microbiome that can be altered in association with chronic respiratory disease. How one maintains a specialized (healthy) microbiome that resists significant fluctuation remains unknown, although smoking, diet, antimicrobial therapy, and infection have all been observed to influence microbial lung homeostasis. In this review, we outline the specific role of polymerizing mucin, a key functional component of the mucus layer that changes during pulmonary disease. We discuss strategies by which mucin feed and spatial orientation directly influence microbial behavior and highlight how a compromised mucus layer gives rise to inflammation and microbial dysbiosis. This emerging field of respiratory research provides fresh opportunities to examine mucus, and its function as predictors of infection risk or disease progression and severity across a range of chronic pulmonary disease states and consider new perspectives in the development of mucolytic treatments.