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Advances in Physiology Education May 2024The movement of air into and out of the lungs is facilitated by changes in pressure within the thoracic cavity relative to atmospheric pressure, as well as the...
The movement of air into and out of the lungs is facilitated by changes in pressure within the thoracic cavity relative to atmospheric pressure, as well as the resistance encountered by airways. In this process, the movement of air into and out of the lungs is driven by pressure gradients established by changes in lung volume and intra-alveolar pressure. However, pressure never sucks! The concept that pressure never sucks, pressure only pushes encapsulates a fundamental principle in the behavior of gases. This concept challenges common misconceptions about pressure, shedding light on the dynamic forces that govern the movement of gases. In this Illumination, we explore the essence of this concept and its applications in pulmonary ventilation. Pressure is one of the most important concepts in physics and physiology. Atmospheric pressure at sea level is equal to 1 atmosphere, or around 101,325 Pascal [Pa (1 Pa = 1 N/m2)]. This huge pressure is pushing down on everything all the time. However, this pressure is difficult to understand because we do not often observe the power of this incredible force. We used five readily available, simple, and inexpensive demonstrations to introduce the physics and power of pressure. This extraordinarily complex physics concept was approached in a straightforward and inexpensive manner while still providing an understanding of the fundamental concepts. These simple demonstrations introduced basic concepts and addressed common misconceptions about pressure.
PubMed: 38813605
DOI: 10.1152/advan.00066.2024 -
Frontiers in Immunology 2024To explore the clinical characteristics and treatment outcomes of children with central nervous system (CNS) involvement in eosinophilic granulomatosis with polyangiitis... (Review)
Review
OBJECTIVE
To explore the clinical characteristics and treatment outcomes of children with central nervous system (CNS) involvement in eosinophilic granulomatosis with polyangiitis (EGPA).
METHODS
A child who presented with EGPA complicated by CNS involvement was admitted to our hospital in June 2023. The clinical features were analyzed retrospectively, and relevant literatures were reviewed to provide a comprehensive overview of this condition.
RESULTS
A ten-year-old girl, who had a history of recurrent cough and asthma accompanied by peripheral blood eosinophilia for eight months, was admitted to our hospital. On admission, spotted papules were visible on her hands and feet, bilateral pulmonary rales were audible. The laboratory examination revealed that the proportion of eosinophils (EOS) exceeded 10% of white blood cells, the anti-neutrophil cytoplasmic antibody (MPO-ANCA) was positive, the immunoglobulin G level was 15.80g/L, and the immunoglobulin E level was greater than 2500.00IU/mL. The imaging examination showed multiple patchy and nodular high-density shadows in both lungs as well as sinusitis. Pulmonary function tests indicated moderate ventilation and diffusion dysfunction. Bone marrow cytology demonstrated a significant increase in the proportion of eosinophils. Skin pathology confirmed leukocytoclastic vasculitis. During the hospitalization, the child had a convulsion. The magnetic resonance imaging (MRI) scan of the brain showed multiple abnormal signal shadows in the bilateral cerebral cortex and the electroencephalogram (EEG) showed epileptic waves. Following the administration of methylprednisolone pulse therapy in combination with cyclophosphamide treatment, her cough and asthma resolved, the skin rash disappeared without any further convulsions. We found that only a young EGPA patient with CNS involvement had been previously reported. The previously reported case began with long-term fever, weight loss, and purpuric rash. Both patients responded well to treatment with glucocorticoids and cyclophosphamide, experiencing significant improvement in their clinical symptoms and normalization of their peripheral blood eosinophils.
CONCLUSION
The diagnosis of EGPA in children can be challenging. When a child is affected by EGPA, it is essential to remain vigilant for signs of CNS involvement. The treatment with glucocorticoids and cyclophosphamide is effective in managing EGPA in children.
Topics: Humans; Female; Child; Churg-Strauss Syndrome; Treatment Outcome; Granulomatosis with Polyangiitis; Cyclophosphamide; Antibodies, Antineutrophil Cytoplasmic
PubMed: 38812515
DOI: 10.3389/fimmu.2024.1406424 -
Jornal Brasileiro de Pneumologia :... May 2024
Challenges in the treatment of cystic fibrosis in the era of CFTR modulatorsAuthors' replyUse of elexacaftor+tezacaftor+ivacaftor in individuals with cystic fibrosis and at least one F508del allele a systematic review and meta-analysisDiscontinuation versus continuation of hypertonic saline or...
Topics: Humans; Cystic Fibrosis; Benzodioxoles; Cystic Fibrosis Transmembrane Conductance Regulator; Aminophenols; Indoles; Quinolones; Pyridines; Pyrazoles; Pyrroles; Saline Solution, Hypertonic; Drug Combinations; Forced Expiratory Volume; Pyrrolidines
PubMed: 38808835
DOI: 10.36416/1806-3756/e20240107 -
Jornal Brasileiro de Pneumologia :... 2024To assess differences in the sputum microbiota of community-acquired pneumonia (CAP) patients with either COPD or asthma, specifically focusing on a patient population...
OBJECTIVE
To assess differences in the sputum microbiota of community-acquired pneumonia (CAP) patients with either COPD or asthma, specifically focusing on a patient population in Turkey.
METHODS
This retrospective study included hospitalized patients > 18 years of age with a diagnosis of pneumonia between January of 2021 and January of 2023. Participants were recruited from two hospitals, and three patient groups were considered: CAP patients with asthma, CAP patients with COPD, and CAP patients without COPD or asthma.
RESULTS
A total of 246 patients with CAP were included in the study, 184 (74.8%) and 62 (25.2%) being males and females, with a mean age of 66 ± 14 years. Among the participants, 52.9% had COPD, 14.2% had asthma, and 32.9% had CAP but no COPD or asthma. Upon analysis of sputum cultures, positive sputum culture growth was observed in 52.9% of patients. The most commonly isolated microorganisms were Pseudomonas aeruginosa (n = 40), Acinetobacter baumannii (n = 20), Klebsiella pneumoniae (n = 16), and Moraxella catarrhalis (n = 8). CAP patients with COPD were more likely to have a positive sputum culture (p = 0.038), a history of antibiotic use within the past three months (p = 0.03), utilization of long-term home oxygen therapy (p < 0.001), and use of noninvasive ventilation (p = 0.001) when compared with the other patient groups. Additionally, CAP patients with COPD had a higher CURB-65 score when compared with CAP patients with asthma (p = 0.004).
CONCLUSIONS
This study demonstrates that CAP patients with COPD tend to have more severe presentations, while CAP patients with asthma show varied microbial profiles, underscoring the need for patient-specific management strategies in CAP.
Topics: Humans; Female; Male; Sputum; Asthma; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Community-Acquired Infections; Aged; Middle Aged; Microbiota; Hospitalization; Turkey; Aged, 80 and over; Pneumonia; Pneumonia, Bacterial
PubMed: 38808825
DOI: 10.36416/1806-3756/e20230329 -
International Journal of Chronic... 2024This study investigated if individuals with chronic obstructive pulmonary disease (COPD) and frailty are more likely to have acute exacerbations of COPD or require... (Comparative Study)
Comparative Study
PURPOSE
This study investigated if individuals with chronic obstructive pulmonary disease (COPD) and frailty are more likely to have acute exacerbations of COPD or require hospitalization for exacerbation than those without frailty.
PATIENTS AND METHODS
Data on 135 outpatients with stable COPD were analyzed with the Cox proportional hazards model to assess the risk of future events. The Kihon Checklist was administered at baseline to classify the participants as robust, pre-frail, or frail. The follow-up period was a maximum of six and a half years.
RESULTS
In all, 76 patients (56.3%) experienced an exacerbation and 46 (34.1%) were hospitalized due to it. Multivariate Cox proportional hazards analysis that accounted for FEV and sex showed that the frail group was more likely to face future risks of COPD exacerbations [Hazard ratio 1.762 (95% CI 1.011-3.070), p=0.046] and hospitalizations for exacerbation [2.238 (1.073-4.667), p=0.032] than the robust group. No significant differences were observed when comparing robust patients to those who were pre-frail or pre-frail to frail either in exacerbations or hospitalizations. When comparing the C-indices for frailty and FEV, the former index (exacerbation 0.591 and hospitalization 0.663) did not exceed the latter (0.663 and 0.769) in either analysis.
CONCLUSION
Frail COPD patients have a more unfavorable future risk of acute exacerbations of COPD and hospitalizations for exacerbation than robust patients. However, no significant differences were observed when comparing robust patients to those who were pre-frail or pre-frail to frail, suggesting that the future risk for COPD patients with frailty is only higher compared to those who are considered robust. Additionally, FEV was found to be a more reliable predictor of future events than measures of frailty.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Male; Female; Aged; Frailty; Disease Progression; Risk Factors; Forced Expiratory Volume; Hospitalization; Frail Elderly; Middle Aged; Lung; Time Factors; Risk Assessment; Aged, 80 and over; Prognosis; Geriatric Assessment
PubMed: 38807967
DOI: 10.2147/COPD.S455316 -
JAMA Network Open May 2024More than 70 000 Medicare beneficiaries receive care in long-term acute care hospitals (LTCHs) annually for prolonged acute illness. However, little is known about...
IMPORTANCE
More than 70 000 Medicare beneficiaries receive care in long-term acute care hospitals (LTCHs) annually for prolonged acute illness. However, little is known about long-term functional and cognitive outcomes of middle-aged and older adults after hospitalization in an LTCH.
OBJECTIVE
To describe survival, functional, and cognitive status after LTCH hospitalization and to identify factors associated with an adverse outcome.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study included middle-aged and older adults enrolled in the Health and Retirement Study (HRS) with linked fee-for-service Medicare claims. Included participants were aged 50 years or older with an LTCH admission between January 1, 2003, and December 31, 2016, with HRS interviews available before admission. Data were analyzed between November 1, 2021, and June 30, 2023.
MAIN OUTCOMES AND MEASURES
Function and cognition were ascertained from HRS interviews conducted every 2 years. The primary outcome was death or severe impairment in the 2.5 years after LTCH hospitalization, defined as dependencies in 2 or more activities of daily living (ADLs) or dementia. Multivariable logistic regression was performed to evaluate associations with a priori selected risk factors including pre-LTCH survival prognosis (Lee index score), pre-LTCH impairment status, and illness severity characterized by receipt of mechanical ventilation and prolonged intensive care unit stay of 3 days or longer.
RESULTS
This study included 396 participants, with a median age of 75 (IQR, 68-82) years. Of the participants, 201 (51%) were women, 125 (28%) had severe impairment, and 318 (80%) died or survived with severe impairment (functional, cognitive, or both) within 2.5 years of LTCH hospitalization. After accounting for acute illness characteristics, prehospitalization survival prognosis as determined by the Lee index score and severe baseline impairment (functional, cognitive, or both) were associated with an increased likelihood of death or severe impairment in the 2.5 years after LTCH hospitalization (adjusted odds ratio [AOR], 3.2 [95% CI, 1.7 to 6.0] for a 5-point increase in Lee index score; and AOR, 4.5 [95% CI, 1.3 to 15.4] for severe vs no impairment).
CONCLUSIONS AND RELEVANCE
In this cohort study, 4 of 5 middle-aged and older adults died or survived with severe impairment within 2.5 years of LTCH hospitalization. Better preadmission survival prognosis and functional and cognitive status were associated with lower risk of an adverse outcome, and these findings should inform decision-making for older adults with prolonged acute illness.
Topics: Humans; Female; Male; Aged; Retrospective Studies; Hospitalization; United States; Middle Aged; Cognition; Aged, 80 and over; Activities of Daily Living; Long-Term Care; Medicare; Risk Factors
PubMed: 38805226
DOI: 10.1001/jamanetworkopen.2024.13309 -
Therapeutic Advances in Respiratory... 2024Bronchial thermoplasty (BT) is a recently developed non-pharmacological therapy for refractory bronchial asthma. Although increasing evidence has suggested that BT is... (Observational Study)
Observational Study
BACKGROUND
Bronchial thermoplasty (BT) is a recently developed non-pharmacological therapy for refractory bronchial asthma. Although increasing evidence has suggested that BT is effective for various phenotypes of severe asthma, its safety and efficacy in patients with severe irreversible impaired lung function are unclear.
OBJECTIVES
To assess the efficacy and safety of BT in patients with refractory asthma, including patients with a severely impaired forced expiratory volume in 1 second (FEV1).
DESIGN
This was a single-center, retrospective, observational cohort study.
METHODS
We retrospectively reviewed the medical records of 15 patients with refractory asthma (Global Initiative for Asthma step 4 or 5), including patients with severely impaired airflow limitation (% predicted pre-bronchodilator FEV1 <60%), who had undergone BT between June 2016 and January 2022. We analyzed the efficacy (change in asthma symptoms, exacerbation rate, pulmonary function, asthma medication, and serum inflammatory chemokine/cytokines before and after BT) and complications in all patients. We compared these data between patients with severe obstructive lung dysfunction [group 1(G1)] and patients with FEV1 ⩾ 60% [group 2 (G2)].
RESULTS
Six patients were in G1 and nine were in G2. Clinical characteristics, T2 inflammation, and concurrent treatment were equivalent in both groups. BT significantly improved asthma-related symptoms (measured using the Asthma Control Test and Asthma Quality of Life Questionnaire scores) in both groups. FEV1 was significantly improved in G1 but not in G2. Four patients in G2, but none in G1, experienced asthma exacerbation requiring additional systemic corticosteroids (including two requiring prolonged hospitalization) after BT. Long-term responders (patients who reduced systemic or inhaled corticosteroid without newly adding biologics in a follow-up > 2 years) of BT were identified in G1 and G2 ( = 2, 33.3% and = 4, 44.4%, respectively).
CONCLUSION
BT in patients with refractory asthma and severe airflow limitation is equally safe and efficacious as that in patients with moderate airflow limitation.
Topics: Humans; Male; Retrospective Studies; Female; Bronchial Thermoplasty; Asthma; Middle Aged; Forced Expiratory Volume; Treatment Outcome; Aged; Severity of Illness Index; Lung; Adult; Recovery of Function; Time Factors; Quality of Life
PubMed: 38804685
DOI: 10.1177/17534666241254980 -
International Journal of Chronic... 2024This phase 1 study (NCT04370873) evaluated safety and pharmacokinetics/pharmacodynamics (PK/PD) of MK-5475 in participants with pulmonary hypertension associated with... (Randomized Controlled Trial)
Randomized Controlled Trial
Phase 1 Study of MK-5475, an Inhaled Soluble Guanylate Cyclase Stimulator, in Participants with Pulmonary Hypertension Associated with Chronic Obstructive Pulmonary Disease.
PURPOSE
This phase 1 study (NCT04370873) evaluated safety and pharmacokinetics/pharmacodynamics (PK/PD) of MK-5475 in participants with pulmonary hypertension associated with COPD (PH-COPD).
METHODS
Eligible participants were 40-80 years old with COPD (FEV/FVC <0.7; FEV >30% predicted) and PH (mean pulmonary arterial pressure ≥25 mmHg). Participants were randomized 2:1 to MK-5475 or placebo via dry-powder inhaler once daily for 7 days in Part 1 (360 µg) or 28 days in Part 2 (380 µg). Safety was assessed by adverse events (AEs) and arterial blood oxygenation. Part-2 participants had pulmonary vascular resistance (PVR; primary PD endpoint) and pulmonary blood volume (PBV; secondary PD endpoint) measured at baseline and Day 28. A non-informative prior was used to calculate posterior probability (PP) that the between-group difference (MK-5475 - placebo) in mean percent reduction from baseline in PVR was less than -15%.
RESULTS
Nine participants were randomized in Part 1, and 14 participants in Part 2. Median age of participants (86.4% male) was 68.5 years (41-77 years); 95.5% had moderate-to-severe COPD. Incidences of AEs were comparable between MK-5475 and placebo: overall (5/14 [36%] versus 5/8 [63%]), drug-related (1/14 [7%] versus 2/8 [25%]), and serious (1/14 [7%] versus 1/8 [13%]). MK-5475 caused no meaningful changes in arterial blood oxygenation or PBV. MK-5475 versus placebo led to numerical improvements from baseline in PVR (-21.2% [95% CI: -35.4, -7.0] versus -5.4% [95% CI: -83.7, 72.9]), with between-group difference in PVR less than -15% and calculated PP of 51%.
CONCLUSION
The favorable safety profile and numerical reductions in PVR observed support further clinical development of inhaled MK-5475 for PH-COPD treatment.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Male; Aged; Administration, Inhalation; Female; Middle Aged; Treatment Outcome; Double-Blind Method; Hypertension, Pulmonary; Adult; Lung; Aged, 80 and over; Soluble Guanylyl Cyclase; Dry Powder Inhalers; Time Factors; Forced Expiratory Volume; Enzyme Activators; Antihypertensive Agents; Arterial Pressure; Vital Capacity
PubMed: 38803412
DOI: 10.2147/COPD.S454905 -
International Journal of Chronic... 2024Reports from Europe and North America suggest that female chronic obstructive pulmonary disease (COPD) patients have a higher symptom burden and mortality than male... (Observational Study)
Observational Study Comparative Study
BACKGROUND
Reports from Europe and North America suggest that female chronic obstructive pulmonary disease (COPD) patients have a higher symptom burden and mortality than male patients. However, little is known about the management reality of female patients with COPD in Japan.
PATIENTS AND METHODS
We compared the clinical characteristics of female COPD patients with those of male using the cohort of the COPD Assessment in Practice study, which is a cross-sectional multicenter observational study.
RESULTS
Of the 1168 patients, 133 (11.4%) were female. A history of never smoking was higher in females than males (p<0.01). Although there was no difference in age or forced expiratory volume in one second (FEV) % predicted between the groups, modified medical research council dyspnea scale (mMRC) and number of frequent exacerbators were higher in females (mMRC≥2: p<0.01; number of exacerbations≥2: p=0.011). The mean forced vital capacity and FEV values in females were lower than those in males (p<0.0001 and p<0.0001, respectively). Females were more likely to use long-term oxygen therapy and inhaled corticosteroids than males (p=0.016 and p<0.01, respectively). The prevalence of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups B, C, D (ABCD GOLD 2017 classification), and E (ABE GOLD 2023 classification) was higher in females than in males.
CONCLUSION
The disease burden of female patients with COPD is higher than that of male patients in Japan, suggesting the importance of interventions considering female-dominant features such as lower absolute FVC and FEV, respiratory failure, and asthma-like conditions.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Female; Cross-Sectional Studies; Japan; Male; Aged; Forced Expiratory Volume; Middle Aged; Sex Factors; Lung; Vital Capacity; Prevalence; Healthcare Disparities; Risk Factors; Oxygen Inhalation Therapy; Disease Progression; Adrenal Cortex Hormones; Treatment Outcome; Smoking; Health Status Disparities; Aged, 80 and over; Bronchodilator Agents
PubMed: 38803411
DOI: 10.2147/COPD.S455397 -
Critical Care (London, England) May 2024Acute respiratory distress syndrome (ARDS) represents a life-threatening inflammatory reaction marked by refractory hypoxaemia and pulmonary oedema. Despite advancements... (Review)
Review
Acute respiratory distress syndrome (ARDS) represents a life-threatening inflammatory reaction marked by refractory hypoxaemia and pulmonary oedema. Despite advancements in treatment perspectives, ARDS still carries a high mortality rate, often due to systemic inflammatory responses leading to multiple organ dysfunction syndrome (MODS). Indeed, the deterioration and associated mortality in patients with acute lung injury (LI)/ARDS is believed to originate alongside respiratory failure mainly from the involvement of extrapulmonary organs, a consequence of the complex interaction between initial inflammatory cascades related to the primary event and ongoing mechanical ventilation-induced injury resulting in multiple organ failure (MOF) and potentially death. Even though recent research has increasingly highlighted the role of the gastrointestinal tract in this process, the pathophysiology of gut dysfunction in patients with ARDS remains mainly underexplored. This review aims to elucidate the complex interplay between lung and gut in patients with LI/ARDS. We will examine various factors, including systemic inflammation, epithelial barrier dysfunction, the effects of mechanical ventilation (MV), hypercapnia, and gut dysbiosis. Understanding these factors and their interaction may provide valuable insights into the pathophysiology of ARDS and potential therapeutic strategies to improve patient outcomes.
Topics: Humans; Respiratory Distress Syndrome; Lung; Respiration, Artificial; Gastrointestinal Tract
PubMed: 38802959
DOI: 10.1186/s13054-024-04966-4