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Physiological Research Sep 2017The respiratory system is constantly exposed to pathogens which enter the lungs by inhalation or via blood stream. Lipopolysaccharide (LPS), also named endotoxin, can... (Review)
Review
The respiratory system is constantly exposed to pathogens which enter the lungs by inhalation or via blood stream. Lipopolysaccharide (LPS), also named endotoxin, can reach the airspaces as the major component of the outer membrane of Gram-negative bacteria, and lead to local inflammation and systemic toxicity. LPS affects alveolar type II (ATII) cells and pulmonary surfactant and although surfactant molecule has the effective protective mechanisms, excessive amount of LPS interacts with surfactant film and leads to its inactivation. From immunological point of view, surfactant specific proteins (SPs) SP-A and SP-D are best characterized, however, there is increasing evidence on the involvement of SP-B and SP-C and certain phospholipids in immune reactions. In animal models, the instillation of LPS to the respiratory system induces acute lung injury (ALI). It is of clinical importance that endotoxin-induced lung injury can be favorably influenced by intratracheal instillation of exogenous surfactant. The beneficial effect of this treatment was confirmed for both natural porcine and synthetic surfactants. It is believed that the surfactant preparations have anti-inflammatory properties through regulating cytokine production by inflammatory cells. The mechanism by which LPS interferes with ATII cells and surfactant layer, and its consequences are discussed below.
Topics: Acute Lung Injury; Animals; Biological Products; Humans; Lipopolysaccharides; Lung; Phospholipids; Pulmonary Surfactants; Swine
PubMed: 28937231
DOI: 10.33549/physiolres.933672 -
European Respiratory Review : An... Sep 2017Idiopathic pulmonary fibrosis (IPF) is characterised by progressive changes of the lung architecture causing cough and dyspnoea and ultimately leading to lung failure... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is characterised by progressive changes of the lung architecture causing cough and dyspnoea and ultimately leading to lung failure and death. Today, for the first time, two drugs that may reduce the inexorable progression of the disease are available, suggesting that treatment with specific drugs for IPF should be started as soon as diagnosis is made. This applies to any disease and particularly to IPF, which is marked by a 5-year survival comparable or even worse than many cancers. However, despite common sense and even worse, in spite of scientific data coming from clinical trials, analysis, long-term safety studies and real-life experiences, the question of when to start and when to stop treatment with antifibrotics is still debated. In IPF, particularly when the disease is diagnosed at an early stage, "wait and watch" behaviour is not rare to observe. This is largely due to the lack of awareness of both patients and clinicians regarding the progression of the disease and its prognosis. Another important issue is when treatment should be stopped. In general, there are two main reasons to stop a therapy: unbearable side-effects and/or lack of efficacy. According to current (although preliminary) evidence, antifibrotic drugs should not be discontinued except for safety issues.
Topics: Clinical Decision-Making; Disease Progression; Drug Administration Schedule; Early Diagnosis; Humans; Idiopathic Pulmonary Fibrosis; Lung; Predictive Value of Tests; Respiratory System Agents; Risk Factors; Time Factors; Treatment Outcome
PubMed: 28974541
DOI: 10.1183/16000617.0053-2017 -
The Clinical Investigator Mar 1993The adult respiratory distress syndrome (ARDS) is characterized by extended inflammatory processes in the lung microvascular, interstitial, and alveolar compartments,... (Review)
Review
The adult respiratory distress syndrome (ARDS) is characterized by extended inflammatory processes in the lung microvascular, interstitial, and alveolar compartments, resulting in vasomotor disturbances, plasma leakage, cell injury, and complex gas exchange disturbances. Abnormalities in the alveolar surfactant system have long been implicated in the pathogenetic sequelae of this life-threatening syndrome. This hypothesis is supported by similarities in pulmonary failure between patients with ARDS and preterm babies with infant respiratory distress syndrome, known to be triggered primarily by lack of surfactant material. Mechanisms of surfactant alterations in ARDS include: (a) lack of surface-active compounds (phospholipids, apoproteins) due to reduced generation/release by diseased pneumocytes or to increased loss of material (this feature includes changes in the relative composition of the surfactant phospholipid and/or apoprotein profiles); (b) inhibition of surfactant function by plasma protein leakage (inhibitory potencies of different plasma proteins have been defined); (c) "incorporation" of surfactant phospholipids and apoproteins into polymerizing fibrin upon hyaline membrane formation; and (d) damage/inhibition of surfactant compounds by inflammatory mediators (proteases, oxidants, nonsurfactant lipids). Alterations in alveolar surfactant function may well contribute to a variety of pathophysiological key events encountered in ARDS. These include decrease in compliance, ventilation-perfusion mismatch including shunt flow due to altered gas flow distribution (atelectasis, partial alveolar collapse, small airway collapse), and lung edema formation. Moreover, more speculative at the present time, surfactant abnormalities may add to a reduction in alveolar host defense competence and an upregulation of inflammatory events under conditions of ARDS. Persistent atelectasis of surfactant-deficient and in particular fibrin-loaded alveoli may represent a key event to trigger fibroblast proliferation and fibrosis in late ARDS ("collapse induration"). Overall, the presently available data on surfactant abnormalities in ARDS lend credit to therapeutic trials with transbronchial surfactant administration. In addition to the classical goals of replacement therapy defined for preterm infants (rapid improvement in lung compliance and gas exchange), this approach will have to consider its impact on host defense competence and inflammatory and proliferative processes when applied in adults with respiratory failure.
Topics: Apoproteins; Humans; Phospholipids; Pulmonary Alveoli; Pulmonary Surfactants; Respiratory Distress Syndrome
PubMed: 8481620
DOI: 10.1007/BF00180100 -
Pulmonary Pharmacology & Therapeutics Oct 2013Cough is a protective reflex and defence mechanism in healthy individuals, which helps clear excessive secretions and foreign material from the lungs. Cough often... (Review)
Review
Cough is a protective reflex and defence mechanism in healthy individuals, which helps clear excessive secretions and foreign material from the lungs. Cough often presents as the first and most persistent symptom of many respiratory diseases and some non-respiratory disorders, but can also be idiopathic, and is a common respiratory complaint for which medical attention is sought. Chronic cough of various aetiologies is a regular presentation to specialist respiratory clinics, and is reported as a troublesome symptom by a significant proportion of the population. Despite this, the treatment options for cough are limited. The lack of effective anti-tussives likely stems from our incomplete understanding of how the tussive reflex is mediated. However, research over the last decade has begun to shed some light on the mechanisms which provoke cough, and may ultimately provide us with better anti-tussive therapies. This review will focus on the in vitro and in vivo models that are currently used to further our understanding of the sensory innervation of the respiratory tract, and how these nerves are involved in controlling the cough response. Central to this are the Transient Receptor Potential (TRP) ion channels, a family of polymodal receptors that can be activated by such diverse stimuli as chemicals, temperature, osmotic stress, and mechanical perturbation. These ion channels are thought to be molecular pain integrators and targets for novel analgesic agents for the treatment of various pain disorders but some are also being developed as anti-tussives.
Topics: Animals; Antitussive Agents; Cough; Drug Design; Drug Evaluation, Preclinical; Humans; Models, Biological; Respiratory System; Respiratory Tract Diseases; Transient Receptor Potential Channels
PubMed: 23474212
DOI: 10.1016/j.pupt.2013.02.007 -
International Journal of Chronic... 2019Chronic airflow limitation is the common denominator of patients with chronic obstructive pulmonary disease (COPD). However, it is not possible to predict morbidity and... (Review)
Review
Chronic airflow limitation is the common denominator of patients with chronic obstructive pulmonary disease (COPD). However, it is not possible to predict morbidity and mortality of individual patients based on the degree of lung function impairment, nor does the degree of airflow limitation allow guidance regarding therapies. Over the last decades, understanding of the factors contributing to the heterogeneity of disease trajectories, clinical presentation, and response to existing therapies has greatly advanced. Indeed, diagnostic assessment and treatment algorithms for COPD have become more personalized. In addition to the pulmonary abnormalities and inhaler therapies, extra-pulmonary features and comorbidities have been studied and are considered essential components of comprehensive disease management, including lifestyle interventions. Despite these advances, predicting and/or modifying the course of the disease remains currently impossible, and selection of patients with a beneficial response to specific interventions is unsatisfactory. Consequently, non-response to pharmacologic and non-pharmacologic treatments is common, and many patients have refractory symptoms. Thus, there is an ongoing urgency for a more targeted and holistic management of the disease, incorporating the basic principles of P4 medicine (predictive, preventive, personalized, and participatory). This review describes the current status and unmet needs regarding personalized medicine for patients with COPD. Also, it proposes a systems medicine approach, integrating genetic, environmental, (micro)biological, and clinical factors in experimental and computational models in order to decipher the multilevel complexity of COPD. Ultimately, the acquired insights will enable the development of clinical decision support systems and advance personalized medicine for patients with COPD.
Topics: Clinical Decision-Making; Comorbidity; Disease Progression; Genetic Predisposition to Disease; Health Status; Humans; Molecular Targeted Therapy; Patient Selection; Phenotype; Precision Medicine; Pulmonary Disease, Chronic Obstructive; Respiratory System Agents; Risk Assessment; Risk Factors; Risk Reduction Behavior; Treatment Outcome
PubMed: 31371934
DOI: 10.2147/COPD.S175706 -
European Respiratory Review : An... Mar 2013This article reviews the most important articles published in interstitial lung disease, as reviewed during the Clinical Year in Review session at the 2012 annual... (Review)
Review
This article reviews the most important articles published in interstitial lung disease, as reviewed during the Clinical Year in Review session at the 2012 annual European Respiratory Society Congress in Vienna, Austria. Since the recent international guidelines for the management of idiopathic pulmonary fibrosis (IPF), important new evidence is available. The anti-fibrotic drug pirfenidone has been recently approved in Europe. Other pharmacological agents, especially nintedanib, are still being tested. The so-called triple combination therapy, anticoagulation therapy and endothelin receptor antagonists, especially ambrisentan, are either harmful or ineffective in IPF and are not recommended as treatment. Although the clinical course of IPF is highly variable, novel tools have been developed for individual prediction of prognosis. Acute exacerbations of IPF are associated with increased mortality and may occur with higher frequency in IPF patients with associated pulmonary hypertension. Interstitial lung disease associated with connective tissue disease has been definitely established to have a better long-term survival than IPF. A subset of patients present with symptoms and/or biological autoimmune features, but do not fulfil diagnostic criteria for a given autoimmune disease; this condition is associated with a higher prevalence of nonspecific interstitial pneumonia pattern, female sex and younger age, although survival relevance is unclear.
Topics: Humans; Idiopathic Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial; Respiratory System Agents; Risk Factors; Sarcoidosis, Pulmonary; Treatment Outcome
PubMed: 23457161
DOI: 10.1183/09059180.00006812 -
Current Opinion in Pharmacology Jun 2018Oxidative stress is implicated in the pathogenesis of respiratory diseases, such as COPD and its comorbidities, asthma, idiopathic pulmonary fibrosis and radiation... (Review)
Review
Oxidative stress is implicated in the pathogenesis of respiratory diseases, such as COPD and its comorbidities, asthma, idiopathic pulmonary fibrosis and radiation pneumonitis. Antioxidants drugs, such as small molecule thiols, nuclear erythroid-2 related factor 2 activators and catalytic enzyme mimetics have been developed to target oxidant-dependent mechanisms. The therapeutic effects of antioxidants have been generally disappointing. A small number of antioxidants are approved for clinical use, such as the small molecule thiol N-acetyl-l-cysteine for chronic obstructive pulmonary disease, and in the United States, the superoxide dismutase mimetic AEOL 10150 for severe radiation pneumonitis. The future use of antioxidants for the treatment of chronic respiratory diseases may require a precision medicine approach to identify responsive patients.
Topics: Animals; Antioxidants; Comorbidity; Drug Design; Drug Discovery; Humans; Lung; Molecular Targeted Therapy; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; Respiratory System Agents; Signal Transduction
PubMed: 29223018
DOI: 10.1016/j.coph.2017.11.013 -
The Lancet. Respiratory Medicine Sep 2013Pneumonia is a widespread and common infectious lung disease that causes inflammation, which can lead to reduced oxygenation, shortness of breath, and death. An... (Review)
Review
Pneumonia is a widespread and common infectious lung disease that causes inflammation, which can lead to reduced oxygenation, shortness of breath, and death. An estimated nearly 1.2 million children younger than 5 years died in 2011 from pneumonia. Most of these deaths occured in developing countries where access to care is limited and interventions that have improved care in developed countries are scarce. Despite substantial increases in our understanding of the clinical syndrome of pneumonia and its aetiologies, its accurate diagnosis is challenging when clinical indicators are relied on, and improves only modestly with addition of laboratory, microbiological, or radiographical tests. Prevention programmes and treatment guidelines have led to impressive reductions in disease, but children remain at risk of misdiagnosis and inadequate treatment. Research to address challenges in the aetiological diagnosis of pneumonia and widespread implementation of treatment interventions beyond vaccines and antibiotics are necessary to mitigate the burden of pneumonia and improve child survival.
Topics: Anti-Bacterial Agents; Child, Preschool; Developing Countries; Drug Therapy, Combination; Humans; Infant; Infant, Newborn; Pneumonia, Bacterial; Pneumonia, Viral; Practice Guidelines as Topic; Respiratory System Agents
PubMed: 24461618
DOI: 10.1016/S2213-2600(13)70075-4 -
European Respiratory Review : An... Mar 2013
Review
Topics: Humans; Hypertension, Pulmonary; Lung; Lung Diseases, Interstitial; Lung Transplantation; Predictive Value of Tests; Respiratory System Agents; Risk Factors; Scleroderma, Systemic; Treatment Outcome
PubMed: 23457159
DOI: 10.1183/09059180.00005512 -
Therapeutic Advances in Respiratory... Apr 2014Nonadherence to inhaled therapies is a major problem in the treatment of cystic fibrosis that can influence lung function and health outcomes. Potential contributors to... (Review)
Review
Nonadherence to inhaled therapies is a major problem in the treatment of cystic fibrosis that can influence lung function and health outcomes. Potential contributors to nonadherence have been identified, including demographic and psychosocial factors, time and convenience of inhaled therapy, and treatment beliefs. Additional research is clearly needed to clarify the contributors and to determine which interventions and technological advances will enhance adherence to inhaled therapies in patients with cystic fibrosis. Nurses and allied health professionals are ideally positioned to assist patients and families with adherence to inhaled therapies through monitoring, communication, and education about the available therapies and their proper use. This review briefly summarizes the available evidence about contributors to nonadherence, potential interventions, novel delivery devices for inhaled therapies, and opportunities for additional research.
Topics: Administration, Inhalation; Cystic Fibrosis; Health Knowledge, Attitudes, Practice; Humans; Medication Adherence; Nebulizers and Vaporizers; Patient Education as Topic; Respiratory System Agents; Treatment Outcome
PubMed: 24594976
DOI: 10.1177/1753465814524471