Semin Respir Crit Care Med
· 2024 Apr · PMID 38211629
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Aspiration pneumonia is a lower respiratory tract infection that results from inhalation of foreign material, often gastric and oropharyngeal contents. It is important to distinguish this from a similar entity, aspiratio...Aspiration pneumonia is a lower respiratory tract infection that results from inhalation of foreign material, often gastric and oropharyngeal contents. It is important to distinguish this from a similar entity, aspiration with chemical pneumonitis, as treatment approaches may differ. An evolving understanding of the human microbiome has shed light on the pathogenesis of aspiration pneumonia, suggesting that dysbiosis, repetitive injury, and inflammatory responses play a role in its development. Risk factors for aspiration events involve a complex interplay of anatomical and physiological dysfunctions in the nervous, gastrointestinal, and pulmonary systems. Current treatment strategies have shifted away from anaerobic organisms as leading pathogens. Prevention of aspiration pneumonia primarily involves addressing oropharyngeal dysphagia, a significant risk factor for aspiration pneumonia, particularly among elderly individuals and those with cognitive and neurodegenerative disorders.
Semin Respir Crit Care Med
· 2024 Feb · PMID 38211628
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Among all clinical manifestations of pulmonary aspergillosis, invasive pulmonary aspergillosis (IPA) is the most acute presentation. IPA is caused by hyphae invading the pulmonary tissue, causing either tracheobronchiti...Among all clinical manifestations of pulmonary aspergillosis, invasive pulmonary aspergillosis (IPA) is the most acute presentation. IPA is caused by hyphae invading the pulmonary tissue, causing either tracheobronchitis and/or bronchopneumonia. The degree of fungal invasion into the respiratory tissue can be seen as a spectrum, going from colonization to deep tissue penetration with angio-invasion, and largely depends on the host's immune status. Patients with prolonged, severe neutropenia and patients with graft-versus-host disease are at particularly high risk. However, IPA also occurs in other groups of immunocompromised and nonimmunocompromised patients, like solid organ transplant recipients or critically ill patients with severe viral disease. While a diagnosis of proven IPA is challenging and often warranted by safety and feasibility, physicians must rely on a combination of clinical, radiological, and mycological features to assess the likelihood for the presence of IPA. Triazoles are the first-choice regimen, and the choice of the drug should be made on an individual basis. Adjunctive therapy such as immunomodulatory treatment should also be taken into account. Despite an improving and evolving diagnostic and therapeutic armamentarium, the burden and mortality of IPA still remains high. This review aims to give a comprehensive and didactic overview of the current knowledge and best practices regarding the epidemiology, clinical presentation, diagnosis, and treatment of acute IPA.
Verweij PE, Song Y, Buil JB
… +2 more, Zhang J, Melchers WJG
Semin Respir Crit Care Med
· 2024 Feb · PMID 38196063
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Aspergilli may cause various pulmonary diseases in humans, including allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), and acute invasive pulmonary aspergillosis (IPA). In addition, c...Aspergilli may cause various pulmonary diseases in humans, including allergic bronchopulmonary aspergillosis (ABPA), chronic pulmonary aspergillosis (CPA), and acute invasive pulmonary aspergillosis (IPA). In addition, chronic colonization may occur in cystic fibrosis (CF). represents the main pathogen, which may employ different morphotypes, for example, conidia, hyphal growth, and asexual sporulation, in the various diseases. These morphotypes determine the ease by which can adapt to stress by antifungal drug exposure, usually resulting in one or more resistance mutations. Key factors that enable the emergence of resistance include genetic variation and selection. The ability to create genetic variation depends on the reproduction mode, including, sexual, parasexual, and asexual, and the population size. These reproduction cycles may take place in the host and/or in the environment, usually when specific conditions are present. Environmental resistance is commonly characterized by tandem repeat (TR)-mediated mutations, while in-host resistance selection results in single-resistance mutations. Reported cases from the literature indicate that environmental resistance mutations are almost exclusively present in patients with IA indicating that the risk for in-host resistance selection is very low. In aspergilloma, single-point mutations are the dominant resistance genotype, while in other chronic diseases, for example, ABPA, CPA, and CF, both TR-mediated and single-resistance mutations are reported. Insights into the pathogenesis of resistance selection in various diseases may help to improve diagnostic and therapeutic strategies.
Póvoa P, Pitrowsky M, Guerreiro G
… +2 more, Pacheco MB, Salluh JIF
Semin Respir Crit Care Med
· 2024 Apr · PMID 38196062
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Community acquired pneumonia (CAP) is a prevalent infectious disease often requiring hospitalization, although its diagnosis remains challenging as there is no gold standard test. In severe CAP, clinical and radiologic c...Community acquired pneumonia (CAP) is a prevalent infectious disease often requiring hospitalization, although its diagnosis remains challenging as there is no gold standard test. In severe CAP, clinical and radiologic criteria have poor sensitivity and specificity, and microbiologic documentation is usually delayed and obtained in less than half of sCAP patients. Biomarkers could be an alternative for diagnosis, treatment monitoring and establish resolution. Beyond the existing evidence about biomarkers as an adjunct diagnostic tool, most evidence comes from studies including CAP patients in primary care or emergency departments, and not only sCAP patients. Ideally, biomarkers used in combination with signs, symptoms, and radiological findings can improve clinical judgment to confirm or rule out CAP diagnosis, and may be valuable adjunctive tools for risk stratification, differentiate viral pneumonia and monitoring the course of CAP. While no single biomarker has emerged as an ideal one, CRP and PCT have gathered the most evidence. Overall, biomarkers offer valuable information and can enhance clinical decision-making in the management of CAP, but further research and validation are needed to establish their optimal use and clinical utility.
Pickens CI, Gao CA, Morales-Nebreda L
… +1 more, Wunderink RG
Semin Respir Crit Care Med
· 2024 Apr · PMID 38196061
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The microbiology of severe community acquired pneumonia (SCAP) has implications on management, clinical outcomes and public health policy. Therefore, knowledge of the etiologies of SCAP and methods to identify these micr...The microbiology of severe community acquired pneumonia (SCAP) has implications on management, clinical outcomes and public health policy. Therefore, knowledge of the etiologies of SCAP and methods to identify these microorganisms is key. Bacteria including Streptococcus pneumoniae, Staphylococcus aureus and Enterobacteriaceae continue to be important causes of SCAP. Viruses remain the most commonly identified etiology of SCAP. Atypical organisms are also important etiologies of SCAP and are critical to identify for public health. With the increased number of immunocompromised individuals, less common pathogens may also be found as the causative agent of SCAP. Traditional diagnostic tests, including semi-quantitative respiratory cultures, blood cultures and urinary antigens continue to hold an important role in the evaluation of patients with SCAP. Many of the limitations of the aforementioned tests are addressed by rapid, molecular diagnostic tests. Molecular diagnostics utilize culture-independent technology to identify species-specific genetic sequences. These tests are often semi-automated and provide results within hours, which provides an opportunity for expedient antibiotic stewardship. The existing literature suggests molecular diagnostic techniques may improve antibiotic stewardship in CAP, and future research should investigate optimal methods for implementation of these assays into clinical practice.
Neuböck MJ, for CPAnet, Günther G
… +7 more, Barac A, Davidsen JR, Laursen CB, Agarwal R, Sehgal IS, Lange C, Salzer HJF
Semin Respir Crit Care Med
· 2024 Feb · PMID 38196060
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Post-tuberculosis lung disease (PTLD) has only recently been put in the spotlight as a medical entity. Recent data suggest that up to 50% of tuberculosis (TB) patients are left with PTLD-related impairment after completi...Post-tuberculosis lung disease (PTLD) has only recently been put in the spotlight as a medical entity. Recent data suggest that up to 50% of tuberculosis (TB) patients are left with PTLD-related impairment after completion of TB treatment. The presence of residual cavities in the lung is the largest risk factor for the development of chronic pulmonary aspergillosis (CPA) globally. Diagnosis of CPA is based on four criteria including a typical radiological pattern, evidence of species, exclusion of alternative diagnosis, and a chronic course of disease. In this manuscript, we provide a narrative review on CPA as a serious complication for patients with PTLD.
Evans TJ, Lawal A, Kosmidis C
… +1 more, Denning DW
Semin Respir Crit Care Med
· 2024 Feb · PMID 38154471
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Chronic pulmonary aspergillosis (CPA) refers to a number of clinical syndromes resulting from the presence and local proliferation of organisms in the lungs of patients with chronic lung disease. CPA is more common than...Chronic pulmonary aspergillosis (CPA) refers to a number of clinical syndromes resulting from the presence and local proliferation of organisms in the lungs of patients with chronic lung disease. CPA is more common than was realized two decades ago. Recognition remains poor, despite recent studies from many countries highlighting the high prevalence in at-risk populations. In low- and middle-income countries, CPA may be misdiagnosed and treated as tuberculosis (TB). In addition, CPA may develop following successful TB treatment. The coronavirus disease pandemic has resulted in significant disruption to provision of TB care, likely leading to more extensive lung damage, which could increase the risk for CPA.Although CPA refers to various syndromes, the classic presentation is that of chronic cavitary pulmonary aspergillosis, which manifests as one or more progressive cavities with or without a fungal ball, accompanied by systemic and respiratory symptoms for at least 3 months. Diagnosis relies on immunoglobulin G in serum, as sputum culture lacks sensitivity. Differential diagnosis includes mycobacterial infection, bacterial lung abscess or necrotizing pneumonia, lung cancer, and endemic fungi.The aim of antifungal treatment in CPA is to improve symptoms and quality of life, and to halt progression, and possibly reverse radiological changes. Current recommendations suggest treatment for 6 months, although in practice many patients remain on long-term treatment. Improvement may manifest as weight gain and improvement of symptoms such as productive cough, hemoptysis, and fatigue. Surgical management should be considered in cases of diagnostic uncertainty, in significant hemoptysis, and when there is concern for lack of response to therapy. Itraconazole and voriconazole are the first-line azoles, with more experience now accumulating with posaconazole and isavuconazole. Side effects are frequent and careful monitoring including therapeutic drug monitoring is essential. Intravenous antifungals such as echinocandins and amphotericin B are used in cases of azole intolerance or resistance, which often develop on treatment. Relapse is seen after completion of antifungal therapy in around 20% of cases, mostly in bilateral, high-burden disease.Several research priorities have been identified, including characterization of immune defects and genetic variants linked to CPA, pathogenetic mechanisms of adaptation in the lung environment, the contribution of non- species, and the role of new antifungal agents, immunotherapy, and combination therapy.
Semin Respir Crit Care Med
· 2024 Feb · PMID 38154470
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Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to airway colonization by in patients with asthma and cystic fibrosis. The pathophysiology of ABPA involves a complex interplay betwe...Allergic bronchopulmonary aspergillosis (ABPA) is a complex hypersensitivity reaction to airway colonization by in patients with asthma and cystic fibrosis. The pathophysiology of ABPA involves a complex interplay between the fungus and the host immune response, which causes persistent inflammation and tissue damage. Patients present with chronic cough, wheezing, and dyspnea due to uncontrolled asthma. Characteristic symptoms include the expectoration of brownish mucus plugs. Radiographic findings often reveal fleeting pulmonary infiltrates, bronchiectasis, and mucus impaction. However, the definitive diagnosis of ABPA requires a combination of clinical, radiological, and immunological findings. The management of ABPA aims to reduce symptoms, prevent disease progression, and minimize the future risk of exacerbations. The treatment approach involves systemic glucocorticoids or antifungal agents to suppress the inflammatory response or fungal growth and prevent exacerbations. Biological agents may be used in patients with severe disease or glucocorticoid dependence. This review provides an overview of the clinical manifestations and current treatment options for ABPA.
Semin Respir Crit Care Med
· 2024 Feb · PMID 38151025
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Currently available and recommended options for the treatment of pulmonary aspergillosis include the triazoles, echinocandins, and amphotericin B products. These therapies have significant limitations. Only the azoles ar...Currently available and recommended options for the treatment of pulmonary aspergillosis include the triazoles, echinocandins, and amphotericin B products. These therapies have significant limitations. Only the azoles are available orally, but their use is often limited by toxicities, drug-drug interactions, pharmacokinetic variability, and emerging resistance. While the echinocandins are safe agents and may have a role in combination therapy, they are unproven as monotherapy. Amphotericin B preparations are toxic and require intensive monitoring. Finally, aspergillosis continues to be a disease conferring substantial morbidity and mortality, and clinical trials have not identified a therapeutic approach clearly associated with improved outcomes. As a result, there is a great need for new options in the treatment of invasive aspergillosis. Ideally, such options would be safe, have high oral bioavailability, have favorable pharmacokinetics to sequestered sites and retain activity against azole-resistant isolates. Reassuringly, there is a robust pipeline of novel therapies in development. Rezafungin (a once-weekly dosed echinocandin) and ibrexafungerp (oral agent with same mechanism of action as echinocandins) will likely be reserved for combination therapy or refractory/intolerance scenarios with no other options. Inhaled opelconazole is an attractive option for combination therapy and prophylaxis of pulmonary aspergillosis. Development of an oral form of amphotericin B that avoids nephrotoxicity and electrolyte disturbances is an exciting development. Finally, olorofim and fosmanogepix, two agents with novel mechanisms of action and oral formulations, hold significant potential to challenge the triazole antifungals place as preferred therapies. However, many questions remain regarding these novel agents, and at the time of this writing, none of these agents have been robustly studied in Phase III studies of aspergillosis, and so their promise remains investigational.
Semin Respir Crit Care Med
· 2023 Oct · PMID 37816346
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With ascent to high altitude, barometric pressure declines, leading to a reduction in the partial pressure of oxygen at every point along the oxygen transport chain from the ambient air to tissue mitochondria. This leads...With ascent to high altitude, barometric pressure declines, leading to a reduction in the partial pressure of oxygen at every point along the oxygen transport chain from the ambient air to tissue mitochondria. This leads, in turn, to a series of changes over varying time frames across multiple organ systems that serve to maintain tissue oxygen delivery at levels sufficient to prevent acute altitude illness and preserve cognitive and locomotor function. This review focuses primarily on the physiological adjustments and acclimatization processes that occur in the lungs of healthy individuals, including alterations in control of breathing, ventilation, gas exchange, lung mechanics and dynamics, and pulmonary vascular physiology. Because other organ systems, including the cardiovascular, hematologic and renal systems, contribute to acclimatization, the responses seen in these systems, as well as changes in common activities such as sleep and exercise, are also addressed. While the pattern of the responses highlighted in this review are similar across individuals, the magnitude of such responses often demonstrates significant interindividual variability which accounts for subsequent differences in tolerance of the low oxygen conditions in this environment.
Semin Respir Crit Care Med
· 2023 Oct · PMID 37816345
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Gas exchange in the lung depends on tidal breathing, which brings new oxygen to and removes carbon dioxide from alveolar gas. This maintains alveolar partial pressures that promote passive diffusion to add oxygen and rem...Gas exchange in the lung depends on tidal breathing, which brings new oxygen to and removes carbon dioxide from alveolar gas. This maintains alveolar partial pressures that promote passive diffusion to add oxygen and remove carbon dioxide from blood in alveolar capillaries. In a lung model without ventilation and perfusion (V̇Q̇) mismatch, alveolar partial pressures of oxygen and carbon dioxide are primarily determined by inspiratory pressures and alveolar ventilation. Regions with shunt or low ratios worsen arterial oxygenation while alveolar dead space and high lung units lessen CO elimination efficiency. Although less common, diffusion limitation might cause hypoxemia in some situations. This review covers the principles of lung gas exchange and therefore mechanisms of hypoxemia or hypercapnia. In addition, we discuss different metrics that quantify the deviation from ideal gas exchange.
Semin Respir Crit Care Med
· 2023 Oct · PMID 37816344
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Full text
The pulmonary circulation is a low-pressure, low-resistance circuit whose primary function is to deliver deoxygenated blood to, and oxygenated blood from, the pulmonary capillary bed enabling gas exchange. The distributi...The pulmonary circulation is a low-pressure, low-resistance circuit whose primary function is to deliver deoxygenated blood to, and oxygenated blood from, the pulmonary capillary bed enabling gas exchange. The distribution of pulmonary blood flow is regulated by several factors including effects of vascular branching structure, large-scale forces related to gravity, and finer scale factors related to local control. Hypoxic pulmonary vasoconstriction is one such important regulatory mechanism. In the face of local hypoxia, vascular smooth muscle constriction of precapillary arterioles increases local resistance by up to 250%. This has the effect of diverting blood toward better oxygenated regions of the lung and optimizing ventilation-perfusion matching. However, in the face of global hypoxia, the net effect is an increase in pulmonary arterial pressure and vascular resistance. Pulmonary vascular resistance describes the flow-resistive properties of the pulmonary circulation and arises from both precapillary and postcapillary resistances. The pulmonary circulation is also distensible in response to an increase in transmural pressure and this distention, in addition to recruitment, moderates pulmonary arterial pressure and vascular resistance. This article reviews the physiology of the pulmonary vasculature and briefly discusses how this physiology is altered by common circumstances.
Condliffe R, Newton R, Bauchmuller K
… +8 more, Bonnett T, Kerry R, Mannings A, Nair A, Selby K, Skinner PP, Wilson VJ, Kiely DG
Semin Respir Crit Care Med
· 2023 Dec · PMID 37729924
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Pulmonary hypertension is characterized by right ventricular impairment and a reduced ability to compensate for hemodynamic insults. Consequently, surgery can be challenging but is increasingly considered in view of avai...Pulmonary hypertension is characterized by right ventricular impairment and a reduced ability to compensate for hemodynamic insults. Consequently, surgery can be challenging but is increasingly considered in view of available specific therapies and improved longer term survival. Optimal management requires a multidisciplinary patient-centered approach involving surgeons, anesthetists, pulmonary hypertension clinicians, and intensivists. The optimal pathway involves risk:benefit assessment for the proposed operation, optimization of pulmonary hypertension and any comorbidities, the appropriate anesthetic approach for the specific procedure and patient, and careful monitoring and management in the postoperative period. Where patients are carefully selected and meticulously managed, good outcomes can be achieved.
Semin Respir Crit Care Med
· 2023 Dec · PMID 37709284
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Extracorporeal life support (ECLS), in particular veno-arterial extracorporeal membrane oxygenation, has emerged as a potentially life-saving treatment modality in patients presenting with pulmonary hypertension and righ...Extracorporeal life support (ECLS), in particular veno-arterial extracorporeal membrane oxygenation, has emerged as a potentially life-saving treatment modality in patients presenting with pulmonary hypertension and right heart failure refractory to conventional treatment. Used mainly as a bridge to lung transplantation, ECLS is also being used occasionally as a bridge to recovery in patients with treatable causes of right heart failure. This review article describes indications, contraindications, techniques, and outcomes of the use of ECLS in patients with PH, focusing on practical aspects in the management of such patients.
Semin Respir Crit Care Med
· 2023 Dec · PMID 37709283
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Pulmonary hypertension (PH) is a common complication of diseases affecting the left heart, mostly found in patients suffering from heart failure, with or without preserved left ventricular ejection fraction. Initially dr...Pulmonary hypertension (PH) is a common complication of diseases affecting the left heart, mostly found in patients suffering from heart failure, with or without preserved left ventricular ejection fraction. Initially driven by a passive increase in left atrial pressure (postcapillary PH), several mechanisms may lead in a subset of patient to significant structural changes of the pulmonary vessels or a precapillary component. In addition, the right ventricle may be independently affected, which results in right ventricular to pulmonary artery uncoupling and right ventricular failure, all being associated with a worse outcome. The differential diagnosis of PH associated with left heart disease versus pulmonary arterial hypertension (PAH) is especially challenging in patients with cardiovascular comorbidities and/or heart failure with preserved ejection fraction (HFpEF). A stepwise approach to diagnosis is proposed, starting with a proper clinical multidimensional phenotyping to identify patients in whom hemodynamic confirmation is deemed necessary. Provocative testing (exercise testing, fluid loading, or simple leg raising) is useful in the cath laboratory to identify patients with abnormal response who are more likely to suffer from HFpEF. In contrast with group 1 PH, management of PH associated with left heart disease must focus on the treatment of the underlying condition. Some PAH-approved targets have been unsuccessfully tried in clinical studies in a heterogeneous group of patients, some even leading to an increase in adverse events. There is currently no approved therapy for PH associated with left heart disease.
Seitler S, Dimopoulos K, Ernst S
… +1 more, Price LC
Semin Respir Crit Care Med
· 2023 Dec · PMID 37595615
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The management of acute medical emergencies in patients with pulmonary hypertension (PH) can be challenging. Patients with preexisting PH can rapidly deteriorate due to right ventricular decompensation when faced with ac...The management of acute medical emergencies in patients with pulmonary hypertension (PH) can be challenging. Patients with preexisting PH can rapidly deteriorate due to right ventricular decompensation when faced with acute physiological challenges that would usually be considered low-risk scenarios. This review considers the assessment and management of acute medical emergencies in patients with PH, encompassing both pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), acknowledging these comprise the more severe groups of PH. Management protocols are described in a systems-based approach. Respiratory emergencies include pulmonary embolism, airways disease, and pneumonia; cardiac emergencies including arrhythmia and chest pain with acute myocardial infarction are discussed, alongside PH-specific emergencies such as pulmonary artery dissection and extrinsic coronary artery compression by a dilated proximal pulmonary artery. Other emergencies including sepsis, severe gastroenteritis with dehydration, syncope, and liver failure are also considered. We propose management recommendations for medical emergencies based on available evidence, international guidelines, and expert consensus. We aim to provide advice to the specialist alongside the generalist, and emergency doctors, nurses, and acute physicians in nonspecialist centers. A multidisciplinary team approach is essential in the management of patients with PH, and communication with local and specialist PH centers is paramount. Close hemodynamic monitoring during medical emergencies in patients with preexisting PH is vital, with early referral to critical care recommended given the frequent deterioration and high mortality in this setting.
Lechartier B, Kularatne M, Jaïs X
… +2 more, Humbert M, Montani D
Semin Respir Crit Care Med
· 2023 Dec · PMID 37595614
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Pulmonary hypertension (PH) is a pathophysiological manifestation of a heterogeneous group of diseases characterized by abnormally elevated pulmonary arterial pressures diagnosed on right heart catheterization. The 2022...Pulmonary hypertension (PH) is a pathophysiological manifestation of a heterogeneous group of diseases characterized by abnormally elevated pulmonary arterial pressures diagnosed on right heart catheterization. The 2022 European Society of Cardiology (ESC) and European Respiratory Society (ERS) Guidelines for the diagnosis and treatment of PH provides a new hemodynamic definition to define PH by lowering the threshold of the mean pulmonary artery pressure (mPAP) to 20 mm Hg. Precapillary PH is thus now defined as a mPAP >20 mm Hg together with a normal pulmonary artery wedge pressure (<15 mm Hg) and an increased pulmonary vascular resistance (>2 Wood Units). The ESC/ERS 2022 Guidelines also introduce a revised clinical classification of PH while retaining its previous distinction between the five groups according to the underlying pathophysiology.
Semin Respir Crit Care Med
· 2023 Oct · PMID 37567252
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The well-known ways in which O and CO (and other gases) are carried in the blood were presented in the preceding chapter. However, what the many available texts about O and CO transport do not emphasize is why knowing ho...The well-known ways in which O and CO (and other gases) are carried in the blood were presented in the preceding chapter. However, what the many available texts about O and CO transport do not emphasize is why knowing how gases are carried in blood matters, and this second, companion, article specifically addresses that critical aspect of gas exchange physiology. During gas exchange, both at the lungs and in the peripheral tissues, it is the shapes and the slopes of the O and CO binding curves that explain almost all of the behaviors of each gas and the quantitative differences observed between them. This conclusion is derived from first principle considerations of the gas exchange processes. Dissociation curve shape and slope differences explain most of the differences between O and CO in both diffusive exchange in the lungs and tissues and convective exchange/transport in, and between, the lungs and tissues. In fact, each of the chapters in this volume describes physiological behavior that depends more or less directly on the dissociation curves of O and CO.