RESUMO
BACKGROUND: Vitamin K is essential for numerous physiological processes, including coagulation, bone metabolism, tissue calcification, and antioxidant activity. Deficiency, prevalent in critically ill ICU patients, impacts coagulation and increases the risk of bleeding and other complications. This review aims to elucidate the metabolism of vitamin K in the context of critical illness and identify a potential therapeutic approach. METHODS: In December 2023, a scoping review was conducted using the PRISMA Extension for Scoping Reviews. Literature was searched in PubMed, Embase, and Cochrane databases without restrictions. Inclusion criteria were studies on adult ICU patients discussing vitamin K deficiency and/or supplementation. RESULTS: A total of 1712 articles were screened, and 13 met the inclusion criteria. Vitamin K deficiency in ICU patients is linked to malnutrition, impaired absorption, antibiotic use, increased turnover, and genetic factors. Observational studies show higher PIVKA-II levels in ICU patients, indicating reduced vitamin K status. Risk factors include inadequate intake, disrupted absorption, and increased physiological demands. Supplementation studies suggest vitamin K can improve status but not normalize it completely. Vitamin K deficiency may correlate with prolonged ICU stays, mechanical ventilation, and increased mortality. Factors such as genetic polymorphisms and disrupted microbiomes also contribute to deficiency, underscoring the need for individualized nutritional strategies and further research on optimal supplementation dosages and administration routes. CONCLUSIONS: Addressing vitamin K deficiency in ICU patients is crucial for mitigating risks associated with critical illness, yet optimal management strategies require further investigation. IMPACT RESEARCH: To the best of our knowledge, this review is the first to address the prevalence and progression of vitamin K deficiency in critically ill patients. It guides clinicians in diagnosing and managing vitamin K deficiency in intensive care and suggests practical strategies for supplementing vitamin K in critically ill patients. This review provides a comprehensive overview of the existing literature, and serves as a valuable resource for clinicians, researchers, and policymakers in critical care medicine.
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Estado Terminal , Deficiência de Vitamina K , Vitamina K , Humanos , Estado Terminal/terapia , Vitamina K/uso terapêutico , Deficiência de Vitamina K/tratamento farmacológico , Unidades de Terapia Intensiva/organização & administraçãoRESUMO
Sarcoidosis is a systemic inflammatory disorder characterized by granuloma formation in various organs. It has been associated with nephrolithiasis. The vitamin K epoxide reductase complex subunit 1 (VKORC1) gene, which plays a crucial role in vitamin K metabolism, has been implicated in the activation of proteins associated with calcification, including in the forming of nephrolithiasis. This study aimed to investigate the VKORC1 C1173T polymorphism (rs9934438) in a Dutch sarcoidosis cohort, comparing individuals with and without a history of nephrolithiasis. Retrospectively, 424 patients with sarcoidosis were divided into three groups: those with a history of nephrolithiasis (Group I: n = 23), those with hypercalcemia without nephrolithiasis (Group II: n = 38), and those without nephrolithiasis or hypercalcemia (Group III: n = 363). Of the 424 sarcoidosis patients studied, 5.4% had a history of nephrolithiasis (Group I), only two of whom possessed no VKORC1 polymorphisms (OR = 7.73; 95% CI 1.79-33.4; p = 0.001). The presence of a VKORC1 C1173T variant allele was found to be a substantial risk factor for the development of nephrolithiasis in sarcoidosis patients. This study provides novel insights into the genetic basis of nephrolithiasis in sarcoidosis patients, identifying VKORC1 C1173T as a potential contributor. Further research is warranted to elucidate the precise mechanisms and explore potential therapeutic interventions based on these genetic findings.
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Nefrolitíase , Polimorfismo de Nucleotídeo Único , Sarcoidose , Vitamina K Epóxido Redutases , Humanos , Feminino , Vitamina K Epóxido Redutases/genética , Masculino , Sarcoidose/genética , Sarcoidose/complicações , Pessoa de Meia-Idade , Nefrolitíase/genética , Fatores de Risco , Adulto , Predisposição Genética para Doença , Estudos Retrospectivos , Idoso , AlelosRESUMO
PURPOSE OF REVIEW: Sarcoidosis is a multiorgan system disease exerting significant impact on biophysical, social, psychological and emotional well-being. Mortality and disability correlate to accessible, timely, expert care for sarcoidosis and its related complications. Across health conditions, positive healthcare interactions and interventions can rehabilitate unfavourable factors tied to concepts of ' frailty' . Here, we set out to introduce concepts related to frailty and their impact in the context of sarcoidosis. RECENT FINDINGS: Studies examining frailty across other multiorgan and single organ-based diseases that mirror organ involvement in sarcoidosis demonstrate findings that bear relevance in sarcoidosis. Namely, factors predisposing a person to frailty are a multifactorial phenomenon which are also reflected in the lived experience of sarcoidosis; and that early diagnosis, intervention and prevention may alter a course towards more favourable health outcomes. SUMMARY: Factors predisposing to frailty in other health conditions may also signal a risk in sarcoidosis. In turn, proactive health preservation - regardless of age - may lead to improved biopsychosocial reserve and health-related quality of life. Fortifying holistic resilience in sarcoidosis is anticipated to reduce risk of the occurrence and prolongation of health-related complications, and facilitate swifter recovery from biophysical complications as well as from psychosocial and emotional stressors.
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Fragilidade , Sarcoidose , Humanos , Fragilidade/epidemiologia , Qualidade de VidaRESUMO
PURPOSE OF REVIEW: Drug use in elderly people is high compared to younger people. Simultaneously, elderly are at greater risk when exposed to environmental substances. It is puzzling therefore, that ageing, as a variable in pharmacological and toxicological processes is not investigated in more depth. Moreover, recent data suggest that molecular manifestations of the ageing process also hallmark the pathogenesis of chronic lung diseases, which may impact pharmacology and toxicology. RECENT FINDINGS: In particular, absorption, distribution, metabolism and excretion (ADME) processes of drugs and toxins alter because of ageing. Polypharmacy, which is quite usual with increasing age, increases the risk of drug-drug interactions. Individual differences in combination of drugs use in conjunction with individual variations in drug metabolizing enzymes can influence lung function. SUMMARY: Exploring exposure throughout life (i.e. during ageing) to potential triggers, including polypharmacy, may avoid lung disease or unexplained cases of lung damage. Understanding of the ageing process further unravels critical features of chronic lung disease and helps to define new protective targets and therapies. Optimizing resilience can be key in pharmacology and toxicology and helps in maintaining healthy lungs for a longer period.
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Pneumopatias , Polimedicação , Idoso , Envelhecimento/metabolismo , Interações Medicamentosas , Humanos , Fenômenos Fisiológicos RespiratóriosRESUMO
PURPOSE OF REVIEW: Sarcoidosis is a chronic multisystemic inflammatory disease of unknown aetiology with a wide range of highly variable clinical manifestations and unpredictable disease course. Sarcoidosis patients may present with specific organ-related symptoms involving functional impairments, and less specific symptoms. The decision whether and when to treat a sarcoidosis patient with pharmacotherapy depends on two major factors: risk of organ failure and/or death and impairment of quality of life. This decision is complex and not standardized. RECENT FINDINGS: Glucocorticoids (GCs) are recommended as initial treatment, when needed. Subsequent GC-sparing alternatives frequently follow. Comorbidities or adverse drug reactions (ADRs) from drugs used in sarcoidosis treatment are sometimes very hard to differentiate from symptoms associated with the disease itself, which may cause diagnostic dilemmas. An ideal approach to minimalize ADRs would involve genetic screening prior to prescribing certain 'high-risk drugs' and therapeutic drug monitoring during treatment. Pharmacogenomic testing aims to guide appropriate selection of medicines, with the potential of reducing unnecessary polypharmacy while improving clinical outcomes. SUMMARY: A multidisciplinary approach to the management of sarcoidosis may avoid unnecessary ADRs. It is important to consider the possibility of drug-induced damage in sarcoidosis, especially if the clinical situation deteriorates after the introduction of a particular drug.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Sarcoidose , Doença Crônica , Comorbidade , Glucocorticoides/efeitos adversos , Humanos , Qualidade de Vida , Sarcoidose/induzido quimicamente , Sarcoidose/diagnóstico , Sarcoidose/tratamento farmacológicoRESUMO
BACKGROUND: The major reasons to treat sarcoidosis are to lower the morbidity and mortality risk or to improve quality of life (QoL). The indication for treatment varies depending on which manifestation is the cause of symptoms: lungs, heart, brain, skin or other manifestations. While glucocorticoids remain the first choice for initial treatment of symptomatic disease, prolonged use is associated with significant toxicity. Glucocorticoid-sparing alternatives are available. The presented treatment guidelines aim to provide guidance to physicians treating the very heterogenous sarcoidosis manifestations. METHODS: A European Respiratory Society Task Force committee composed of clinicians, methodologists and patients with experience in sarcoidosis developed recommendations based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology. The committee developed eight PICO (Patients, Intervention, Comparison, Outcomes) questions and these were used to make specific evidence-based recommendations. RESULTS: The Task Force committee delivered 12 recommendations for seven PICOs. These included treatment of pulmonary, cutaneous, cardiac and neurologic disease as well as fatigue. One PICO question regarding small-fibre neuropathy had insufficient evidence to support a recommendation. In addition to the recommendations, the committee provided information on how they use alternative treatments, when there was insufficient evidence to support a recommendation. CONCLUSIONS: There are many treatments available to treat sarcoidosis. Given the diverse nature of the disease, treatment decisions require an assessment of organ involvement, risk for significant morbidity, and impact on QoL of the disease and treatment.
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Qualidade de Vida , Sarcoidose , Fadiga , Humanos , Sarcoidose/diagnóstico , Sarcoidose/terapiaRESUMO
PURPOSE OF REVIEW: Critical review on the notion that exposure to pesticides and herbicides lead to adverse effects in pulmonary health. RECENT FINDINGS: The lung effects of several chemical classes of pesticides and herbicides is biologically plausible. However, the studies that describe the association between exposure and toxic lung effects have numerous limitations. Critical evaluation of the studies that are performed shows that assessment of occupational or environmental exposure to pesticides and herbicides is cumbersome. Moreover, the health effects are not always clearly established due to the use of questionnaires and self-reported data instead of lung function measurements or diagnostic work-up by physicians.Future studies should preferably better characterize the exposure. Genetic phenotyping should be included to understand and strengthen possible (individual) associations between exposure and health outcome. It should be realized that combined exposure to multiple environmental chemicals may lead to different health effects than exposure to individual chemicals. SUMMARY: The relation between exposure to pesticides and herbicides and lung toxicity is less clear than generally assumed. Adverse lung effects seem multifactorial and needs further research. Preventive measures remain key.
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Herbicidas , Exposição Ocupacional , Praguicidas , Exposição Ambiental/efeitos adversos , Herbicidas/toxicidade , Humanos , Exposição Ocupacional/efeitos adversos , Praguicidas/toxicidadeRESUMO
PURPOSE OF REVIEW: The current review focuses on serious pulmonary toxicity after inhalation of over the counter available pyrethroid-based insecticides. Pyrethroid is a synthetic product of pyrethrin, which in turn is the active ingredient of pyrethrum, a flower extract. RECENT FINDINGS: On the contrary, a large gap of knowledge exists in the association of interstitial lung disease (ILD) with pyrethroids. So far, two cases of ILD, one associated with pyrethrin and one associated with pyrethrum, were described. Existing literature on both other (pulmo)toxic effects of pyrethroids in human and animals is summarized. SUMMARY: We present three cases of severe pulmonary toxicity after inhalation of pyrethroid-based insecticides demanding hospitalization and oxygen therapy. One of these cases died. Although a causal relationship was hard to establish, these cases all demonstrated an obvious history of (repeated) pyrethroid exposure associated with ILD. Moreover, other causes of ILD as well as infections were excluded. Furthermore, studies in mammals as well as aquatic animals confirm (pulmonary) toxicity of pyrethroids. The occurrence of toxicity is dose-dependent but also associated with individual susceptibility. Therefore, we would like to acknowledge that awareness of potential hazards of commercially available insecticides containing pyrethroids to both medical physicians and the public is mandatory.
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Inseticidas , Piretrinas , Administração por Inalação , Animais , Humanos , Inseticidas/toxicidade , Piretrinas/toxicidadeRESUMO
Rationale: Socioeconomic factors are associated with worse disease severity at presentation in sarcoidosis, but the relative importance of socioeconomic variables on morbidity and disease burden has not been fully elucidated.Objectives: To determine the association between income and sarcoidosis outcomes after controlling for socioeconomic and disease-related factors.Methods: Using the Sarcoidosis Advanced Registry for Cures database, we analyzed data from 2,318 patients with sarcoidosis in the United States to determine the effect of income and other variables on outcomes. We divided comorbidities arising after diagnosis into those likely related to steroid use and those likely related to sarcoidosis. We assessed the development of health-related, functional, and socioeconomic outcomes following the diagnosis of sarcoidosis.Measurements and Main Results: In multivariate analysis, low-income patients had significantly higher rates of new sarcoidosis-related comorbidities (<$35,000, odds ratio [OR], 2.4 [1.7-3.3]; $35,000-84,999, OR, 1.4 [1.1-1.9]; and ≥$85,000 [reference (Ref)]) and new steroid-related comorbidities (<$35,000, OR, 1.3 [0.9-2.0]; $35,000-84,999, OR, 1.5 [1.1-2.1]; and ≥$85,000 [Ref]), had lower health-related quality of life as assessed by the Sarcoidosis Health Questionnaire (P < 0.001), and experienced more impact on family finances (<$35,000, OR, 7.9 [4.9-12.7]; $35,000-84,999, OR, 2.7 [1.9-3.9]; and ≥$85,000 [Ref]). The use of supplemental oxygen, need for assistive devices, and job loss were more common in lower income patients. Development of comorbidities after diagnosis of sarcoidosis occurred in 63% of patients and were strong independent predictors of poor outcomes. In random forest modeling, income was consistently a leading predictor of outcome.Conclusions: These results suggest the burden from sarcoidosis preferentially impacts the economically disadvantaged.
Assuntos
Efeitos Psicossociais da Doença , Hospitalização/estatística & dados numéricos , Renda/estatística & dados numéricos , Oxigenoterapia/estatística & dados numéricos , Qualidade de Vida , Sarcoidose/fisiopatologia , Desemprego/estatística & dados numéricos , Adulto , Negro ou Afro-Americano , Cardiomiopatias/epidemiologia , Doenças do Sistema Nervoso Central/epidemiologia , Dor Crônica/epidemiologia , Comorbidade , Depressão/epidemiologia , Síndrome de Fadiga Crônica/epidemiologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hipertensão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Análise Multivariada , Obesidade/epidemiologia , Razão de Chances , Pobreza , Fatores de Risco , Sarcoidose/tratamento farmacológico , Sarcoidose/epidemiologia , Tecnologia Assistiva/estatística & dados numéricos , Apneia Obstrutiva do Sono/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Fatores Socioeconômicos , Estados Unidos/epidemiologia , População BrancaRESUMO
Background: The diagnosis of sarcoidosis is not standardized but is based on three major criteria: a compatible clinical presentation, finding nonnecrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. There are no universally accepted measures to determine if each diagnostic criterion has been satisfied; therefore, the diagnosis of sarcoidosis is never fully secure.Methods: Systematic reviews and, when appropriate, meta-analyses were performed to summarize the best available evidence. The evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation approach and then discussed by a multidisciplinary panel. Recommendations for or against various diagnostic tests were formulated and graded after the expert panel weighed desirable and undesirable consequences, certainty of estimates, feasibility, and acceptability.Results: The clinical presentation, histopathology, and exclusion of alternative diagnoses were summarized. On the basis of the available evidence, the expert committee made 1 strong recommendation for baseline serum calcium testing, 13 conditional recommendations, and 1 best practice statement. All evidence was very low quality.Conclusions: The panel used systematic reviews of the evidence to inform clinical recommendations in favor of or against various diagnostic tests in patients with suspected or known sarcoidosis. The evidence and recommendations should be revisited as new evidence becomes available.
Assuntos
Cardiomiopatias/diagnóstico , Nefropatias/diagnóstico , Hepatopatias/diagnóstico , Sarcoidose Pulmonar/diagnóstico , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Aspartato Aminotransferases/sangue , Biópsia , Broncoscopia , Cálcio/sangue , Cardiomiopatias/sangue , Cardiomiopatias/fisiopatologia , Creatinina/sangue , Ecocardiografia , Eletrocardiografia , Eletrocardiografia Ambulatorial , Endossonografia , Oftalmopatias/diagnóstico , Oftalmopatias/fisiopatologia , Humanos , Hipercalcemia/sangue , Hipercalcemia/diagnóstico , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Nefropatias/sangue , Hepatopatias/sangue , Linfonodos/patologia , Linfadenopatia , Imageamento por Ressonância Magnética , Mediastino , Tomografia por Emissão de Pósitrons , Pneumologia , Sarcoidose/sangue , Sarcoidose/diagnóstico , Sarcoidose/patologia , Sarcoidose/fisiopatologia , Sarcoidose Pulmonar/sangue , Sarcoidose Pulmonar/patologia , Sarcoidose Pulmonar/fisiopatologia , Sociedades Médicas , Vitamina D/sangueRESUMO
PURPOSE OF REVIEW: The aim of this article is to describe the known health disparities that exist among patients with sarcoidosis by socioeconomic status, race, and gender, review potential contributors to health disparities in sarcoidosis, investigate the intersectionality among socioeconomic status, race, and gender in sarcoidosis, and outline a research agenda to address these disparities. RECENT FINDINGS: Recent studies have reported the significant financial strain a diagnosis of sarcoidosis has on individuals and the disproportionate affect the strain has on low socioeconomic status individuals, Blacks, and females. Worse dyspnea, lower health-related quality of life, and higher rates of mortality and hospitalization are more common among those who are Black, female, or of low socioeconomic status. SUMMARY: Health disparities in sarcoidosis by socioeconomic status, race, and gender have been described for decades. In this review, we describe potential contributors to health disparities including stress and propose interventions to address disparities including creating educational programs accessible for low-income patients and caregivers, targeting medication adherence and trust in physicians and the medical system, and ensuring access to high-quality care for all patients. As clinicians and researchers, we owe it to our patients to not only describe the health disparities that exist but also stimulate to achieve improvement in sarcoidosis.
Assuntos
Disparidades em Assistência à Saúde/etnologia , Hospitalização/estatística & dados numéricos , Qualidade de Vida , Sarcoidose/epidemiologia , Classe Social , Determinantes Sociais da Saúde , Negro ou Afro-Americano , Dispneia/fisiopatologia , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/estatística & dados numéricos , Humanos , Sarcoidose/mortalidade , Sarcoidose/fisiopatologia , Sarcoidose/terapia , Fatores Sexuais , Fatores Socioeconômicos , Estados Unidos , População BrancaRESUMO
PURPOSE OF REVIEW: Idiopathic pulmonary fibrosis (IPF) is a terminal lung disease of largely unknown cause. Gastroesophageal reflux disease (GERD) was recently discovered to be a trigger for the development of IPF. The current pharmaceutical approach to IPF falls short and there is a pressing need for improved therapeutic options. The present review describes the currently available knowledge regarding the role of oxidative stress and inflammation in the pathophysiology of IPF and GERD and determines the potential use of antioxidants as a treatment option for GERD-associated IPF. RECENT FINDINGS: IPF and GERD share a similar pathophysiology, as oxidative stress and inflammation play a pivotal role in both conditions. This raises the question whether antioxidant treatment could be a well-tolerated and effective means to alleviate at least some of the symptoms of both conditions. In IPF, antioxidant supplementation complements the inadequately working antioxidant defense system of the lung, reducing oxidative stress and inflammation. In GERD, antioxidants increase levels of endogenous antioxidants, decrease pepsin and gastric acid production, lipid peroxidation, and ulceration, and alleviate subsequent damage to the gastric mucosa. SUMMARY: The increased comorbidity of GERD in IPF patients makes it clear that there is a connection between GERD and IPF. As current treatment options are still inadequate to improve the condition and increase the survival rate of IPF patients, alternative treatment options are crucial. Based on the reviewed scientific evidence, antioxidant supplementation could complement standard IPF treatment, certainly in GERD-associated IPF.
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Antioxidantes/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Refluxo Gastroesofágico/complicações , Humanos , Fibrose Pulmonar Idiopática/etiologiaRESUMO
Neurosarcoidosis (NS) is an often severe, destructive manifestation with a likely under-reported prevalence of 5 to 15% of sarcoidosis cases, and in its active phase demands timely treatment intervention. Clinical signs and symptoms of NS are variable and wide-ranging, depending on anatomical involvement. Cranial nerve dysfunction, cerebrospinal parenchymal disease, aseptic meningitis, and leptomeningeal disease are the most commonly recognized manifestations. However, non-organ-specific potentially neurologically driven symptoms, such as fatigue, cognitive dysfunction, and small fiber neuropathy, appear frequently.Heterogeneous clinical presentations and absence of any single conclusive test or biomarker render NS, and sarcoidosis itself, a challenging definitive diagnosis. Clinical suspicion of NS warrants a thorough systemic and neurologic evaluation hopefully resulting in supportive extraneural physical exam and/or tissue findings. Treatment targets the severity of the manifestation, with careful discernment of whether NS reflects active potentially reversible inflammatory granulomatous disease versus inactive postinflammatory damage whereby functional impairment is unlikely to be pharmacologically responsive. Non-organ-specific symptoms are poorly understood, challenging in deciphering reversibility and often identified too late to respond to conventional immunosuppressive/pharmacological treatment. Physical therapy, coping strategies, and stress reduction may benefit patients with all disease activity levels of NS.This publication provides an approach to screening, diagnosis, disease activity discernment, and pharmacological as well as nonpharmacological treatment interventions to reduce disability and protect health-related quality of life in NS.
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Biomarcadores/análise , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/terapia , Sarcoidose/diagnóstico , Sarcoidose/terapia , Doenças do Sistema Nervoso Central/sangue , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Diagnóstico Precoce , Humanos , Imunossupressores/uso terapêutico , Imageamento por Ressonância Magnética , Modalidades de Fisioterapia , Qualidade de Vida , Sarcoidose/sangue , Sarcoidose/líquido cefalorraquidianoRESUMO
Drugs are serious but underestimated causative agents of interstitial lung disease (ILD). Both cytotoxic and immune mechanisms may be involved in drug-induced ILD (DI-ILD). We aimed to investigate whether polymorphisms of relevant CYP enzymes involved in the metabolization of tamsulosin might explain the pathologic mechanism of the DI-ILD in the cases with suspected tamsulosin DI-ILD. We collected 22 tamsulosin-associated DI-ILD cases at two ILD Expertise Centers in the Netherlands between 2009 and 2020. CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP3A5 single nucleotide polymorphisms were genotyped and compared with a control group of 78 healthy Caucasian male volunteers. Nine cases were phenotyped as CYP2D6 poor metabolizers and 13 as CYP2D6 intermediate metabolizers. The phenotypes of the cases differed significantly from those of the healthy controls, with more poor metabolizers. After withdrawal of tamsulosin, the pulmonary condition of three cases had improved, six patients had stabilized, and one patient stabilized after reducing the tamsulosin dose. The described 22 cases suggest that an association between the presence of CYP2D6 allelic variants and tamsulosin-associated ILD is highly likely. These cases highlight the importance of both clinical and genetic risk stratification aimed to achieve a more accurate prevention of DI-ILD in the future and enhance the quality of life of patients.
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Citocromo P-450 CYP2D6/genética , Doenças Pulmonares Intersticiais/patologia , Tansulosina/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Citocromo P-450 CYP2D6/metabolismo , Genótipo , Humanos , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/genética , Masculino , Fenótipo , Polimorfismo de Nucleotídeo Único , Tansulosina/metabolismoRESUMO
PURPOSE OF REVIEW: Sarcoidosis is a complex disease with many faces, and the clinical manifestation and course of neurosarcoidosis are particularly variable. Although neurosarcoidosis occurs in up to 10% of sarcoidosis patients, it can lead to significant morbidity and some mortality. RECENT FINDINGS: Three criteria are usually required for a diagnosis of (neuro)sarcoidosis: clinical and radiologic manifestations, noncaseating granulomas, and no evidence of alternative disease. Recent guidelines have helped to clarify criteria for diagnosing neurosarcoidosis. No firm guidelines exist on whether, when, and how treatment should be started. Treatment depends on the presentation and distribution, extensiveness, and severity of neurosarcoidosis. As regards evidence-based treatment, only a few randomized controlled trials have been done. Hence, several aspects of (neuro)sarcoidosis management are not fully addressed by the current literature. SUMMARY: Significant advances have been made in the potential and accuracy of diagnostics for neurosarcoidosis. Treatment should be approached within the context of the patient's anticipated clinical course, avoidance of adverse drug effects, and, if necessary, from the perspective of the comprehensive management of a chronic disease. A multidisciplinary approach to the management of sarcoidosis is strongly recommended.
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Doenças do Sistema Nervoso Central/terapia , Sarcoidose/terapia , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/psicologia , Gerenciamento Clínico , Humanos , Equipe de Assistência ao Paciente , Sarcoidose/diagnóstico , Sarcoidose/psicologiaRESUMO
PURPOSE OF REVIEW: The diagnosis of drug-induced interstitial lung disease (DI-ILD) is challenging and mainly made by exclusion of other possible causes. Toxicity can occur as a cause of drug(s) or drug-drug interactions. In this review, we summarize the possible role of pharmacogenetics of metabolizing enzymes in DI-ILD. RECENT FINDINGS: Knowledge of the genetic predispositions of enzymes involved in drug metabolization and their relation with proposed cytotoxic mechanisms of DI-ILD, in particular direct cell toxicity and free oxygen radical production is increasing. The cytochrome P450 enzyme family and other enzymes play an important role in the metabolism of all sorts of ingested, injected, or inhaled xenobiotic substances. The liver is the major site for metabolism. Metabolic cytotoxic mechanisms have however also been detected in lung tissue. Polymorphisms in genes coding for enzymes that influence metabolic activity may lead to localized (toxic) reactions and tissue damage. This knowledge may be helpful in preventing the risk of DI-ILD. SUMMARY: Drug toxicity can be the consequence of absence or very poor enzyme activity, especially if no other metabolic route is available. In the case of reduced enzyme activity, it is recommended to reduce the dose or to prescribe an alternative drug, which is metabolized by a different, unaffected enzyme system to prevent toxic side effects. However, enhanced enzyme activity may lead to excessive formation of toxic and sometimes reactive metabolites. Therefore, knowing a patient's drug-metabolizing profile before drug prescription is a promising way to prevent or explain DI-ILD.
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Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Doenças Pulmonares Intersticiais/induzido quimicamente , Farmacogenética/métodos , Xenobióticos/efeitos adversos , Interações Medicamentosas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Humanos , Doenças Pulmonares Intersticiais/diagnósticoRESUMO
BACKGROUND: Consequences of sarcoidosis are wide ranging, and the symptom burden has a great impact on patients' quality of life (QoL). However, the QoL of couples living with sarcoidosis has not yet been studied. OBJECTIVES: Our aim was to assess the QoL of couples living with sarcoidosis and to evaluate whether living with a partner with sarcoidosis influences the partner's QoL. Furthermore, we aimed to assess whether nonspecific symptoms (fatigue, cognitive failure, small fiber neuropathy (SFN)-related symptoms, depressive symptoms, and state/trait anxiety) predict QoL of partners as well as sarcoidosis patients. METHOD: Sarcoidosis outpatients, recruited at Maastricht University Medical Centre (n = 443), and their partners (n = 208) completed several questionnaires, including the World Health Organization QoL - BREF, Fatigue Assessment Scale, SFN screening list, and cognitive failure questionnaire. RESULTS: QoL of the partners as well as the sarcoidosis patients was reduced compared with healthy controls, especially regarding the physical health domain. All nonspecific symptoms studied, as well as perceived social support, predicted one or more QoL domains in the sarcoidosis patients, but these factors did not predict the QoL of their partners. CONCLUSIONS: The QoL of partners of sarcoidosis patients was reduced, although to a lesser extent than that of the patients. Although the nonspecific symptoms and perceived social support were related to the patients' QoL, this was not the case for the partners. In the management of sarcoidosis, it is important to focus not only on the patients but also on their partners.
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Sarcoidose Pulmonar/psicologia , Adulto , Idoso , Estudos Epidemiológicos , Características da Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Cônjuges/psicologia , Adulto JovemRESUMO
Here, we describe a Dutch family with idiopathic pulmonary fibrosis (IPF). We hypothesized that there might be an association between the presence of Vitamin K epoxide reductase complex 1 (VKORC1) and/or cytochrome P450 2C9 (CYP2C9) variant alleles and the early onset of IPF in the members of this family. VKORC1 (rs9923231 and rs9934438) and CYP2C9 (rs1799853 and rs1057910) were genotyped in this family, which includes a significant number of pulmonary fibrosis patients. In all family members, at least one of the variant alleles tested was present. The presence of the VKORC1 variant alleles in all of the IPF cases and CYP2C9 variants in all but one, which likely leads to a phenotype that is characterized by the early onset and progressive course of IPF. Our findings indicate a role of these allelic variants in (familial) IPF. Therefore, we suggest that the presence of these variants, in association with other pathogenic mutations, should be evaluated during genetic counselling. Our findings might have consequences for the lifestyle of patients with familial IPF in order to prevent the disease from becoming manifest.
Assuntos
Citocromo P-450 CYP2C9/genética , Fibrose Pulmonar Idiopática/genética , Polimorfismo de Nucleotídeo Único , Vitamina K Epóxido Redutases/genética , Adulto , Idade de Início , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Linhagem , Regiões Promotoras Genéticas , Estudos RetrospectivosRESUMO
Although chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) seem to be opposite entities from a clinical perspective, common initial pathogenic steps have been suggested in both lung diseases. Emphysema is caused by an elastase/anti-elastase imbalance leading to accelerated elastin degradation. Elastinolysis is however, also accelerated in the IPF patients' lungs. The amino acids desmosine and isodesmosine (DES) are unique to elastin. During the degradation process, elastases liberate DES from elastin fibers. Blood DES levels consequently reflect the rate of systemic elastinolysis and are increased in COPD. This is the first report describing elevated DES levels in IPF patients. We also demonstrated that the age-related increment of DES concentrations is enhanced in IPF. Our current study suggests that elastinolysis is a shared pathogenic step in both COPD and IPF. Further investigation is required to establish the relevance of accelerated elastin degradation in IPF and to determine whether decelerating this process leads to slower progression of lung fibrosis and better survival for patients with IPF.