ARDS is a heterogeneous syndrome that encompasses lung injury from both direct and indirect sources. Direct ARDS (pneumonia, aspiration) has been hypothesized to cause more severe lung epithelial injury than indirect ARDS (eg, nonpulmonary sepsis); however, this hypothesis has not been well studied in humans.

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease. Until recently, the standard therapy for this disease has been essentially supportive, with the exception of a minority of patients who were eligible for lung transplantation. The development pathway for novel medications for IPF has been complicated. There have been several challenges, including an incomplete understanding of the pathogenesis, unpredictable clinical course, lack of validated biomarkers, the low clinical predictive value of animal models of lung injury, and the need to commit to large clinical trials of long duration to obtain initial evidence of clinical efficacy. Despite these challenges, the combination of recent advances in translational medicine and the unprecedented increase in clinical data accumulated from recent large clinical trials has stimulated an increase in the number of clinical development programs for IPF. Clinical programs are increasingly characterized by rational target selection, preclinical optimization of therapeutic molecules, and an emphasis on efficient clinical trial design. A lower rate of functional decline in patients treated with pirfenidone and nintedanib was demonstrated in large clinical trials. In October 2014, these two drugs became the first agents to be approved by the US Food and Drug Administration for the treatment of IPF. (Pirfenidone had already been approved in several countries outside the United States.) In November 2014, the European Medicines Agency approved the use of nintedanib for IPF. The landscape for management of IPF has markedly changed with the advent of approved therapeutic options for IPF. In this article, we review the strategies that are being used to increase the likelihood of success in clinical development programs of novel disease-modifying agents in IPF.

The first of this two-part series on critical illness in pregnancy dealt with obstetric disorders. In Part II, medical conditions that commonly affect pregnant women or worsen during pregnancy are discussed. ARDS occurs more frequently in pregnancy. Strategies commonly used in nonpregnant patients, including permissive hypercapnia, limits for plateau pressure, and prone positioning, may not be acceptable, especially in late pregnancy. Genital tract infections unique to pregnancy include chorioamnionitis, group A streptococcal infection causing toxic shock syndrome, and polymicrobial infection with streptococci, staphylococci, and Clostridium perfringens causing necrotizing vulvitis or fasciitis. Pregnancy predisposes to VTE; D-dimer levels have low specificity in pregnancy. A ventilation-perfusion scan is preferred over CT pulmonary angiography in some situations to reduce radiation to the mother's breasts. Low-molecular-weight or unfractionated heparins form the mainstay of treatment; vitamin K antagonists, oral factor Xa inhibitors, and direct thrombin inhibitors are not recommended in pregnancy. The physiologic hyperdynamic circulation in pregnancy worsens many cardiovascular disorders. It increases risk of pulmonary edema or arrhythmias in mitral stenosis, heart failure in pulmonary hypertension or aortic stenosis, aortic dissection in Marfan syndrome, or valve thrombosis in mechanical heart valves. Common neurologic problems in pregnancy include seizures, altered mental status, visual symptoms, and strokes. Other common conditions discussed are aspiration of gastric contents, OSA, thyroid disorders, diabetic ketoacidosis, and cardiopulmonary arrest in pregnancy. Studies confined to pregnant women are available for only a few of these conditions. We have, therefore, reviewed pregnancy-specific adjustments in the management of these disorders.

Recent emphasis has been placed on methods to predict fluid responsiveness, but the usefulness of using fluid boluses to increase cardiac index in critically ill patients with ineffective circulation or oliguria remains unclear.

Managing critically ill obstetric patients in the ICU is a challenge because of their altered physiology, different normal ranges for laboratory and clinical parameters in pregnancy, and potentially harmful effects of drugs and interventions on the fetus. About 200 to 700 women per 100,000 deliveries require ICU admission. A systematic five-step approach is recommended to enhance maternal and fetal outcomes: (1) differentiate between medical and obstetric disorders with similar manifestations, (2) identify and treat organ dysfunction, (3) assess maternal and fetal risk from continuing pregnancy and decide if delivery/termination of pregnancy will improve outcome, (4) choose an appropriate mode of delivery if necessary, and (5) optimize organ functions for safe delivery. A multidisciplinary team including the intensivist, obstetrician, maternal-fetal medicine specialist, anesthesiologist, neonatologist, nursing specialist, and transfusion medicine expert is key to optimize outcomes. Severe preeclampsia and its complications, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and amniotic fluid embolism, which cause significant organ failure, are reviewed. Obstetric conditions that were not so common in the past are increasingly seen in the ICU. Thrombotic thrombocytopenic purpura of pregnancy is being diagnosed more frequently. Massive hemorrhage from adherent placenta is increasing because of the large number of pregnant women with scars from previous cesarean section. With more complex fetal surgical interventions being performed for congenital disorders, maternal complications are increasing. Ovarian hyperstimulation syndrome is also becoming common because of treatment of infertility with assisted reproduction techniques. Part II will deal with common medical disorders and their management in critically ill pregnant women.

To better understand clinical and epidemiologic patterns of blastomycosis, we report on a large series of blastomycosis in Indiana.

Inhalation/smoking has become the most common method of recreational opiate consumption in the United Kingdom and other countries. Although some heroin smokers appear to develop COPD, little is known about the association.

In recent years, the potentially adverse role of sleep-disordered breathing in cancer incidence and outcomes has emerged. In parallel, animal models of intermittent hypoxia (IH) and sleep fragmentation (SF) emulating the two major components of OSA have lent support to the notion that OSA may enhance the proliferative and invasive properties of solid tumors. Based on several lines of evidence, we propose that OSA-induced increases in sympathetic outflow and alterations in immune function are critically involved in modifying oncologic processes including angiogenesis. In this context, we suggest that OSA, via IH (and potentially SF), promotes changes in several signaling pathways and transcription factors that coordinate malignant transformation and expansion, disrupts host immunologic surveillance, and consequently leads to increased probability of oncogenesis, accelerated tumor proliferation, and invasion, ultimately resulting in adverse outcomes.

Long-term outcomes after stepping down asthma medications are not well described.