Seminars in Respiratory and Critical Care Medicine

In cystic fibrosis, a new era has started with the approval and use of highly effective cystic fibrosis transport regulator (CFTR) modulator therapy. As pulmonary function is increasing and exacerbation rate significantly decreases, the current meaning of fungal pulmonary diseases is questioned. During the past couple of decades, several studies have been conducted regarding fungal colonization and infection of the airways in people with cystic fibrosis. Although Aspergillus fumigatus for filamentous fungi and Candida albicans for yeasts remain by far the most common fungal species in patients with cystic fibrosis, the pattern of fungal species associated with cystic fibrosis has considerably diversified recently...

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Nontuberculous mycobacteria (NTM) are a group of mycobacteria which represent opportunistic pathogens that are of increasing concern in people with cystic fibrosis (pwCF). The acquisition has been traditionally though to be from environmental sources, though recent work has suggested clustered clonal infections do occur and transmission potential demonstrated among pwCF attending CF specialist centers. Guidelines for the screening, diagnosis, and identification of NTM and management of pwCF have been published...

Progressive obstructive lung disease secondary to chronic airway infection, coupled with impaired host immunity, is the leading cause of morbidity and mortality in cystic fibrosis (CF). Classical pathogens found in the airways of persons with CF (pwCF) include Pseudomonas aeruginosa, Staphylococcus aureus, the Burkholderia cepacia complex, Achromobacter species, and Haemophilus influenzae. While traditional respiratory-tract surveillance culturing has focused on this limited range of pathogens, the use of both comprehensive culture and culture-independent molecular approaches have demonstrated complex highly personalized microbial communities...

Diagnosing cystic fibrosis (CF) in adulthood is not a rare occurrence for CF centers despite the popular belief that the diagnosis is achieved almost universally in childhood by means of newborn screening or early clinical presentation. The purpose of this review article is to highlight specific considerations of adult diagnosis of CF. Obtaining a diagnosis of CF at any age is exceptionally important to ensure optimal treatment, monitoring, and support. In the new era of more personalized treatment with the advent of transformative therapies targeting the underlying protein defect, accurate diagnosis is of increasing importance...

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have changed the clinical landscape of cystic fibrosis (CF) by improving clinically significant outcome measures and quality of life of people with CF (pwCF). There are now long-term data showing improved 5-year survival with the use of ivacaftor, and the field continues to evolve at a rapid pace with the continued development of highly effective CFTR modulators. While the randomized controlled trials of CFTR modulators excluded patients with severe lung disease (forced expiratory volume in 1 second <40% predicted), observational data based on case reports and registry data show similar benefits in those with advanced lung disease...

With the improving survival of cystic fibrosis (CF) patients and the advent of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) therapy, the clinical spectrum of this complex multisystem disease continues to evolve. One of the most important clinical events for patients with CF in the course of this disease is acute pulmonary exacerbation (PEx). Clinical and microbial epidemiology studies of CF PEx continue to provide important insight into the disease course, prognosis, and complications...

Timely and accurate data on the epidemiology of sepsis is essential to inform public policy, clinical practice, and research priorities. Recent studies have illuminated several ongoing questions about sepsis epidemiology, including the incidence and outcomes of sepsis in non-Western countries and in specialized populations such as surgical patients, patients with cancer, and the elderly. There have also been new insights into the limitations of current surveillance methods using administrative data and increasing experience tracking sepsis incidence and outcomes using "big data" approaches that take advantage of detailed electronic health record data...

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic has led to an unprecedented public health crisis. The collective global response has led to production of multiple safe and effective vaccines utilizing novel platforms to combat the virus that have propelled the field of vaccinology forward. Significant challenges to universal vaccine effectiveness remain, including immune evasion by SARS-CoV-2 variants, waning of immune response, inadequate knowledge of correlates of protection, and dosing in special populations...

Post-COVID conditions continue to afflict patients long after acute severe acute respiratory syndrome-coronavirus-2 (SARS CoV-2) infection. Over 50 symptoms across multiple organ systems have been reported, with pulmonary, cardiovascular, and neuropsychiatric sequelae occurring most frequently. Multiple terms have been used to describe post-COVID conditions including long COVID, long-haul COVID, postacute coronavirus disease 2019 (COVID-19), postacute sequelae of SARS-CoV-2 infection, long-term effects of COVID, and chronic COVID-19; however, standardized assessments and treatment algorithms for patients have generally been lacking...

The coronavirus disease 2019 (COVID-19) pandemic led to a remarkably rapid development of a range of effective prophylactic vaccines, including new technologies that had not previously been approved for human use. In contrast, the development of new small molecule antiviral therapeutics has taken years to produce the first approved drugs specifically targeting severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), with the intervening years filled with attempts to repurpose existing drugs and the development of biological therapeutics...

Coronavirus disease 2019 (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in significant mortality in pandemic proportions. Inflammation in response to the infection contributes to the pathogenesis of pneumonia. This review will discuss prior studies on the use of glucocorticoids to treat respiratory infections, the rationale for the use glucocorticoids in COVID-19, and review of existing data. We will also highlight outstanding research questions for future studies...

This paper discusses mechanisms of hypoxemia and interventions to oxygenate critically ill patients with COVID-19 which range from nasal cannula to noninvasive and mechanical ventilation. Noninvasive ventilation includes continuous positive airway pressure ventilation (CPAP) and high-flow nasal cannula (HFNC) with or without proning. The evidence for each of these modalities is discussed and thereafter, when to transition to mechanical ventilation (MV). Various techniques of MV, again with and without proning, and rescue strategies which would include extra corporeal membrane oxygenation (ECMO) when it is available and permissive hypoxemia where it is not, are discussed...

The spectrum of disease severity and the insidiousness of clinical presentation make it difficult to recognize patients with coronavirus disease 2019 (COVID-19) at higher risk of worse outcomes or death when they are seen in the early phases of the disease. There are now well-established risk factors for worse outcomes in patients with COVID-19. These should be factored in when assessing the prognosis of these patients. However, a more precise prognostic assessment in an individual patient may warrant the use of predictive tools...

The coronavirus disease 2019 (COVID-19) pandemic has affected individuals of all ages across. Although children generally experience a benign illness from COVID-19, the emergence of novel variants of the virus has resulted in significant changes in the morbidity and mortality rates for this age group. Currently, COVID-19 is the eighth leading cause of pediatric deaths in the United States. In addition to acute respiratory illness, some children can develop a severe postinfectious condition known as a multisystem inflammatory syndrome in children, which can progress to rapid-onset cardiogenic shock...

Pregnancy is an independent risk factor for morbidity and mortality in coronavirus disease 2019 (COVID-19) with increased rates of operative delivery, intensive care unit admission, and mechanical ventilation as well as a possible increased risk of death, independent of other risk factors, compared with nonpregnant women with COVID-19. Furthermore, pregnancy outcomes are worse in those with COVID-19 with increased risk for preeclampsia, venous thromboembolism, preterm birth, miscarriage, and stillbirth compared with pregnant women without COVID-19...

Despite effective antiretroviral therapy (ART), HIV infected individuals throughout the world remain at significant risk of respiratory infections and non-communicable disease. Severe disease from SARS-CoV-2 is associated with a hyperinflammatory phenotype which manifests in the lungs as pneumonia and in some cases can lead to acute respiratory failure. Progression to severe COVID-19 is associated with comorbid disease such as obesity, diabetes mellitus and cardiovascular disease, however data concerning the associated risks of HIV coinfection are still conflicting, with large population studies demonstrating poorer outcomes, whilst smaller, case-controlled studies showing better outcomes...

The coronavirus disease 2019 (COVID-19) pandemic has caused a devastating impact on morbidity and mortality around the world. Severe acute respiratory syndrome-coronavirus-2 has a characteristic tropism for the cardiovascular system by entering the host cells and binding to angiotensin-converting enzyme 2 receptors, which are expressed in different cells, particularly endothelial cells. This endothelial injury is linked by a direct intracellular viral invasion leading to inflammation, microthrombosis, and angiogenesis...

Community-acquired pneumonia (CAP) is a significant cause of morbidity and mortality, one of the most common reasons for infection-related death worldwide. Causes of CAP include numerous viral, bacterial, and fungal pathogens, though frequently no specific organism is found. Beginning in 2019, the COVID-19 pandemic has caused incredible morbidity and mortality. COVID-19 has many features typical of CAP such as fever, respiratory distress, and cough, and can be difficult to distinguish from other types of CAP...

An outbreak of severe pneumonia of unknown cause was identified in Wuhan, China in December 2019: the causative agent was a novel betacoronavirus, severe acute respiratory syndrome-cotonavirus-2 (SARS-CoV-2), a virus that joins a list of coronaviruses causing severe (e.g., SARS and Middle East respiratory syndrome) or milder (e.g., 229E, OC43, NL63, and HKU1) respiratory tract infection. The World Health Organization (WHO) classified the spreading outbreak as a pandemic on March 11, 2020. Many SARS-related coronaviruses (SARSr-CoVs) have been identified in bats, particularly in Rhinolophus horseshoe bats, animals that are common in southern China and Southeast Asia...