Seminars in respiratory and critical care medicine
-
Cystic fibrosis (CF) lung disease is characterized by the development of progressive bronchiectasis and impaired lung function with severe airflow obstruction. CF patients suffer from shortened life expectancy, primarily driven by respiratory failure. ⋯ Although all CF patients are at increased risk for pulmonary complications including hemoptysis, pneumothorax, pulmonary hypertension, and chronic hypoxic and hypercapnic respiratory failure, the risk of developing these complications increases with progression of lung disease. The focus of this article is to summarize the pathophysiology, epidemiology, and management of these key pulmonary complications.
-
Semin Respir Crit Care Med · Dec 2019
ReviewCystic Fibrosis Diagnosis in Newborns, Children, and Adults.
The diagnosis of cystic fibrosis (CF) has traditionally relied on the presence of clinical features of the disease. Today, diagnosis through newborn screening (NBS) is becoming the standard of modern CF care. CF NBS programs can identify CF prior to clinical presentation, but for the advantages of an early diagnosis to accrue a scrupulous system must be in place to ensure all steps in the program are performing. ⋯ In addition to clinical symptoms or positive NBS results, sweat test and genetic analysis are cornerstones in the diagnosis of CF, but in some cases the diagnosis cannot be confirmed on genetic or sweat testing. Difficult diagnosis may be supported by in vivo or ex vivo electrophysiology measurements on respiratory or intestinal epithelia. This can be done by either measuring transepithelial nasal potential difference or intestinal current measurements.
-
Semin Respir Crit Care Med · Dec 2019
ReviewTreating the Underlying Cystic Fibrosis Transmembrane Conductance Regulator Defect in Patients with Cystic Fibrosis.
Detailed knowledge of how mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene disturb the trafficking or function of the CFTR protein and the use of high-throughput drug screens have allowed novel therapeutic strategies for cystic fibrosis (CF). The main goal of treatment is slowly but surely shifting from symptomatic management to targeting the underlying CFTR defect to halt disease progression and even to prevent occurrence of CF complications. CFTR potentiators for patients with class III mutations, mutation R117H (and in United States also for patients with specific residual function mutations) and the combination of a CFTR modulator plus a potentiator for patients homozygous for F508del, are the two classes of modulators that are in use in the clinic. ⋯ In addition, we discuss the entire pipeline of CFTR modulators: novel potentiators and correctors, amplifiers, stabilizers, and read-through agents. Furthermore, we discuss other strategies to improve CFTR function like nonsense-mediated decay inhibitors, modified transfer ribonucleic acids, antisense oligonucleotides, and genetic therapies. CFTR modulators are already changing the face of CF and the pipeline of new therapies continues to be exciting.
-
Semin Respir Crit Care Med · Oct 2019
ReviewPain and Delirium in Critical Illness: An Exploration of Key 2018 SCCM PADIS Guideline Evidence Gaps.
Managing pain and delirium are crucial to patients, families, and caregivers in intensive care units. The Society of Critical Care Medicine 2018 Pain, Agitation/Sedation, Delirium, Immobility, and Sleep disruption (PADIS) guidelines reviewed literature until October 2015 and made its recommendations for critically-ill adults. This chapter addresses evidence gaps, identified during the guideline process, most relevant to clinicians, adds newer evidence published after the PADIS 2018 guidelines were produced, describes hindsight-driven PADIS process or content-related gaps, and reflects on how these considerations may help inform future research investigations and new guideline efforts.
-
Semin Respir Crit Care Med · Oct 2019
ReviewThe Long and Winding Road to Personalized Glycemic Control in the Intensive Care Unit.
In the critically ill adult, dysglycemia is a marker of disease severity and is associated with worse clinical outcomes. Close monitoring of glucose and use of insulin in critically ill patients have been done for more than 2 decades, but the appropriate target glycemic range in critically ill patients remains controversial. Physiological stress response, levels of inflammatory cytokines, nutritional intake, and level of mobility affect glycemic control, and a more personalized approach to patients with dysglycemia is warranted in critically ill intensive care unit (ICU) patients. We discuss the pathophysiology and downstream effects of altered glycemic response in critical illness, management of glycemic control in the ICU, and future strategies toward personalization of critical care glycemic management.