Update on the pharmacological treatment of chronic obstructive pulmonary disease.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a common syndrome associated with smoking and environmental exposures coupled with genetic susceptibility. Recent major advancements in the treatment of COPD patients have become available. AREAS COVERED: New data on the role of classic bronchodilators, including short-acting and long-acting beta2-agonists and anti-muscarinic antagonists, in the treatment of COPD patients are discussed. Data promoting a more targeted approach to inhaled and systemic corticosteroid use in COPD are reviewed. Phosphodiesterase (PDE) inhibitors, including the recently approved PDE 3/4 inhibitor inhaled ensifentrine, are noted. Selective use of antibiotics can play a role in complex COPD patients. COPD patients with evidence of asthma-COPD overlap syndrome and type-two lymphocytic inflammatory-mediated airway constriction appear to respond to biologics, particularly the anti-IL-4/IL-3 antagonist monoclonal antibody, dupilumab. EXPERT OPINION: New therapeutic options have made the approach and treatment of the COPD patient much more complicated. These options tend to be very expensive. Attention to identifying the endotype and phenotype will help direct the pharmacotherapy.

Emerging pharmacological options in the treatment of idiopathic pulmonary fibrosis (IPF).

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a progressive-fibrosing lung disease with a median survival of less than 5 years. Currently, two agents, pirfenidone and nintedanib are approved for this disease, and both have been shown to reduce the rate of decline in lung function in patients with IPF. However, both have significant adverse effects and neither completely arrest the decline in lung function. AREAS COVERED: Thirty experimental agents with unique mechanisms of action that are being evaluated for the treatment of IPF are discussed. These agents work through various mechanisms of action, these include inhibition of transcription nuclear factor k-B on fibroblasts, reduced expression of metalloproteinase 7, the generation of more lysophosphatidic acids, blocking the effects of transforming growth factor ß, and reducing reactive oxygen species as examples of some unique mechanisms of action of these agents. EXPERT OPINION: New drug development has the potential to expand the treatment options available in the treatment of IPF patients. It is expected that the adverse drug effect profiles will be more favorable than current agents. It is further anticipated that these new agents or combinations of agents will arrest the fibrosis, not just slow the fibrotic process.

ZLN005 improves the protective effect of mitochondrial function on alveolar epithelial cell aging by upregulating PGC-1α.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal pulmonary interstitial disease that usually occurs in the elderly. The senescence of alveolar epithelial cells (AECs) is an important mechanism of IPF. The AECs of patients with IPF have lower expression of peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1α), which has been shown to play an important role in maintaining mitochondrial morphology and energy metabolism. This study sought to explore the mechanism by which ZLN005 improves mitochondrial function by upregulating PGC-1α to protect AECs from aging. Methods: Western blot was used to detect the expression of PGC-1α, mitochondrial synthesis protein nuclear respiratory factor-1 (NRF-1), and p21WAF1 in the lung tissue of the IPF patients and the mice with bleomycin (BLM)-induced pulmonary fibrosis. A549 cells and mice AEC2 cells were treated with hydrogen peroxide (H2O2) to construct cell senescence models. Cell senescence was detected by senescence-associated beta-galactosidase staining. The mitochondrial respiratory function was measured, including the adenosine triphosphate (ATP) generation, reactive oxygen species (ROS) level, changes in cell membrane potential, and energy metabolism. Using lentivirus as a vector and using gene editing technology to over express (upPGC-1α) and knockdown PGC-1α (shPGC-1α) in the A549 cells. The PGC-1α agonist ZLN005 was used to pretreat the A549 and shPGC-1α A549 cells, and cell aging and mitochondrial respiratory function were observed. Results: The Western blot and immunofluorescence assays showed that the expression of PGC-1α and NRF-1 was decreased in the lung tissues of the IPF patients and BLM-induced mice pulmonary fibrosis model, while the expression of p21WAF1 was increased. The results of the immunofluorescence and mitochondrial function experiments also indicated that the expression of PGC-1α and mitochondrial synthesis protein NRF-1 were decreased in the senescent cells. Further, the mitochondrial morphology was abnormal and the mitochondrial function was impaired. PGC-1α was involved in the AEC senescence by regulating mitochondrial morphology and function. Treatment with the agonist of PGC-1α (i.e., ZLN005) blocked the H2O2-induced cell senescence by enhancing the expression of PGC-1α. Conclusions: These results provide preliminary insights into the potential clinical application of ZLN005 as a novel therapeutic agent for the treatment of IPF.

A Least Absolute Shrinkage and Selection Operator-Derived Predictive Model for Postoperative Respiratory Failure in a Heterogeneous Adult Elective Surgery Patient Population.

BACKGROUND: Postoperative respiratory failure (PRF) is associated with increased hospital charges and worse patient outcomes. Reliable prediction models can help to guide postoperative planning to optimize care, to guide resource allocation, and to foster shared decision-making with patients. RESEARCH QUESTION: Can a predictive model be developed to accurately identify patients at high risk of PRF? STUDY DESIGN AND METHODS: In this single-site proof-of-concept study, we used structured query language to extract, transform, and load electronic health record data from 23,999 consecutive adult patients admitted for elective surgery (2014-2021). Our primary outcome was PRF, defined as mechanical ventilation after surgery of > 48 h. Predictors of interest included demographics, comorbidities, and intraoperative factors. We used logistic regression to build a predictive model and the least absolute shrinkage and selection operator procedure to select variables and to estimate model coefficients. We evaluated model performance using optimism-corrected area under the receiver operating curve and area under the precision-recall curve and calculated sensitivity, specificity, positive and negative predictive values, and Brier scores. RESULTS: Two hundred twenty-five patients (0.94%) demonstrated PRF. The 18-variable predictive model included: operations on the cardiovascular, nervous, digestive, urinary, or musculoskeletal system; surgical specialty orthopedic (nonspine); Medicare or Medicaid (as the primary payer); race unknown; American Society of Anesthesiologists class ≥ III; BMI of 30 to 34.9 kg/m2; anesthesia duration (per hour); net fluid at end of the operation (per liter); median intraoperative FIO2, end title CO2, heart rate, and tidal volume; and intraoperative vasopressor medications. The optimism-corrected area under the receiver operating curve was 0.835 (95% CI,0.808-0.862) and the area under the precision-recall curve was 0.156 (95% CI, 0.105-0.203). INTERPRETATION: This single-center proof-of-concept study demonstrated that a structured query language extract, transform, and load process, based on readily available patient and intraoperative variables, can be used to develop a prediction model for PRF. This PRF prediction model is scalable for multicenter research. Clinical applications include decision support to guide postoperative level of care admission and treatment decisions.

The pharmacotherapeutics of sarcoidosis.

INTRODUCTION: Sarcoidosis is a multi-system, inflammatory, and granulomatous disease that can damage multiple organs. Several drugs have been used to treat sarcoidosis, but few have randomized-controlled trials (RCTs) to understand their efficacy. This lack of RCTs and the heterogenous nature of sarcoidosis makes for a challenge to the provider caring for these patients. AREAS COVERED: Glucocorticoids remain the backbone of treatment of sarcoidosis. The side effect profile of glucocorticoids has resulted in the search for other sarcoid disease modifying drugs. This paper reviews the pharmacology, history, efficacy data, and adverse effects of alternative treatments. Most alternative sarcoidosis immune modulating treatments lack RCTs to evaluate their relative efficacy. EXPERT OPINION: Because of the variability of disease presentation and progression, the treatment of sarcoidosis is best managed by expert clinicians with a firm understanding of the pharmacology, pharmacokinetics, monitoring requirements, counter-indications, and adverse effects of agents used. More RCTs that compare agents in well-defined sarcoid subgroups are clearly needed.

Pharmacotherapeutic management of asthma in the elderly patient.

INTRODUCTION: Asthma is a heterogeneous syndrome with variable phenotypes. Reversible airway obstruction and airway hyper-responsiveness often with an atopic or eosinophilic component is common in the elderly asthmatic. Asthma chronic obstructive pulmonary disease overlap syndrome (ACOS), a combination of atopy-mediated airway hyper-responsiveness and a history of smoking or other environmental noxious exposures, can lead to some fixed airway obstruction and is also common in elderly patients. Little specific data exist for the treating the elderly asthmatic, thus requiring the clinician to extrapolate from general adult data and asthma treatment guidelines. AREAS COVERED: A stepwise approach to pharmacotherapy of the elderly patient with asthma and ACOS is offered and the literature supporting the use of each class of drugs reviewed. EXPERT OPINION: Inhaled, long-acting bronchodilators in combination with inhaled corticosteroids represent the backbone of treatment for the elderly patient with asthma or ACOS . Beyond these medications used as direct bronchodilators and topical anti-inflammatory agents, a stepwise approach to escalation of therapy includes multiple options such as oral leukotriene receptor antagonist or 5-lipoxygense inhibitor therapy, oral phosphodiesterase inhibitors, systemic corticosteroids, oral macrolide antibiotics and if evidence of eosinophilic/atopic component disease exists then modifying monoclonal antibody therapies.

The pharmacological management of asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS).

Introduction: Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is a disease phenotype that shares T helper lymphocyte cell Th1/neutrophilic/non-Type-2 Inflammation pathways thought to be key in COPD and Th2/eosinophilic/Type-2 inflammatory pathways of asthma. The pharmacology of treating ACOS is challenging in severe circumstances.Areas covered: This review evaluates the stepwise treatment of ACOS using pharmacological treatments used in both COPD and asthma. The most common medications involve the same inhalers used to treat COPD and asthma patients. Advanced stepwise therapies for ACOS patients are based on patient characteristics and biomarkers. Very few clinical trials exist that focus specifically on ACOS patients.Expert opinion: After inhalers, advanced therapies including phosphodiesterase inhibitors, macrolides, N-acetylcysteine and statin therapy for those ACOS patients with a COPD appearance and exacerbations are available. In atopic ACOS patients with exacerbations, advanced asthma therapies (leukotriene receptor antagonists and synthesis blocking agents.) are used. ACOS patients with elevated blood eosinophil/IgE levels are considered for immunotherapy or therapeutic monoclonal antibodies blocking specific Th2/Type-2 interleukins or IgE. Symptom control, stabilization/improvement in pulmonary function and reduced exacerbations are the metrics of success. More pharmacological trials of ACOS patients are needed to better understand which patients benefit from specific treatments.Abbreviations: 5-LOi: 5-lipoxygenase inhibitor; ACOS: asthma - COPD overlap syndrome; B2AR: Beta2 adrenergic receptors; cAMP: cyclic adenosine monophosphate; cGMP: cyclic guanosine monophosphate; CI: confidence interval; COPD: chronic obstructive pulmonary disease; CRS : chronic rhinosinusitis; cys-LT: cysteinyl leukotrienes; DPI: dry powder inhaler; EMA: European Medicines Agency; FDA: US Food and Drug Administration; FDC: fixed-dose combination; FeNO: exhaled nitric oxide; FEV1: forced expiratory volume in one second; FVC: forced vital capacity; GM-CSF: granulocyte-macrophage colony-stimulating factor; ICS : inhaled corticosteroids; IL: interleukin; ILC2: Type 2 innate lymphoid cells; IP3: Inositol triphosphate; IRR: incidence rate ratio; KOLD: Korean Obstructive Lung Disease; LABA: long-acting B2 adrenergic receptor agonist; LAMA: long-acting muscarinic receptor antagonist; LRA: leukotriene receptor antagonist; LT: leukotrienes; MDI: metered-dose inhalers; MN: M-subtype muscarinic receptors; MRA: muscarinic receptor antagonist; NAC: N-acetylcysteine; NEB: nebulization; OR: odds ratio; PDE: phosphodiesterase; PEFR: peak expiratory flow rate; PGD2: prostaglandin D2; PRN: as needed; RR: risk ratio; SABA: short-acting B2 adrenergic receptor agonist; SAMA: short-acting muscarinic receptor antagonist; SDMI: spring-driven mist inhaler; Th1: T helper cell 1 lymphocyte; Th2: T helper cell 2 lymphocytes; TNF-α: tumor necrosis factor alpha; US : United States.

Paradigms in chronic obstructive pulmonary disease: phenotypes, immunobiology, and therapy with a focus on vascular disease.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous syndrome that represents a major global health burden. COPD phenotypes have recently emerged based on large cohort studies addressing the need to better characterize the syndrome. Though comprehensive phenotyping is still at an early stage, factors such as ethnicity and radiographic, serum, and exhaled breath biomarkers have shown promise. COPD is also an immunological disease where innate and adaptive immune responses to the environment and tobacco smoke are altered. The frequent overlap between COPD and other systemic diseases, such as cardiovascular disease, has influenced COPD therapy, and treatments for both conditions may lead to improved patient outcomes. Here, we discuss current paradigms that center on improving the definition of COPD, understanding the immunological overlap between COPD and vascular inflammation, and the treatment of COPD-with a focus on comorbid cardiovascular disease.

Chronic eosinophilic pneumonia presenting with ipsilateral pleural effusion: a case report.

BACKGROUND: Chronic eosinophilic pneumonia is a rare idiopathic interstitial lung disease. The nearly pathognomonic radiographic finding is the peripheral distribution of alveolar opacities. Pleural effusions are rarely seen. We report a case of chronic eosinophilic pneumonia with transudative eosinophilic pleural effusion. CASE PRESENTATION: A 57-year-old Hispanic woman, a nonsmoker with a history of controlled asthma, presented to the hospital with unresolving pneumonia despite three rounds of antibiotics over a 2-month period. She was later diagnosed with chronic eosinophilic pneumonia based on the presence of peripheral blood eosinophilia, the peripheral distribution of alveolar infiltrates on chest radiograph, and a lung parenchymal biopsy with infiltrates of eosinophils. Upon presentation, our patient had a right-sided moderate-sized pleural effusion. The pleural fluid profile was consistent with a transudative effusion with eosinophil predominance. Our patient responded promptly to oral corticosteroid treatment in a few days. The pulmonary infiltrates and pleural effusion subsided on a 1-month follow-up chest radiograph after starting corticosteroid treatment. CONCLUSIONS: We report the first case of chronic eosinophilic pneumonia presenting with pneumonia with ipsilateral transudative eosinophilic pleural effusion. Like other cases of chronic eosinophilic pneumonia, early recognition and diagnosis is essential and prompt treatment with corticosteroids is the mainstay of therapy. Pleural effusion resolved without the further need for therapeutic thoracentesis.

The Changing Drug Culture: Medical and Recreational Marijuana.

The major psychoactive compounds in marijuana (cannabis) are cannabinoids, the most significant of which is delta-9-tetrahydrocannabinol. There are also two synthetic pharmaceutical cannabinoids, nabilone and dronabinol, available by prescription in the United States. The use of marijuana has increased in the United States with passage of medical marijuana laws in many states and legalization of recreational marijuana use in several states. In addition, the potency of marijuana has increased in recent years. Marijuana has been used for a variety of medical purposes, including management of nausea and vomiting, appetite and immunologic stimulation in patients with HIV infection and AIDS, glaucoma, neurologic disorders, and pain relief. Studies on the benefits of marijuana as a treatment for various conditions have been inconsistent, except for those on pain management. Marijuana has adverse effects, and has been associated with driving impairment, psychosis, dependence and withdrawal syndromes, hyperemesis, acute cardiac events, some cancers, and impaired lung function. As with studies on the benefits of marijuana, studies of adverse effects have yielded inconsistent results. Except for impaired driving and the occurrence of dependence and withdrawal syndromes, the adverse effects of marijuana use have not been fully studied.

The Changing Drug Culture: Use and Misuse of Appearance- and Performance-Enhancing Drugs.

Awareness of the prevalence of the use of appearance- and performance-enhancing drugs (APEDs) is increasing. Users range from professional athletes and bodybuilders to amateurs and adolescents. Anabolic androgenic steroids (AASs) are the most widely used APEDs, typically for purposes of building muscle mass, in forms that include pills, injections, topical preparations, and transdermal systems. AASs are often used in combination with augmenting drugs taken to enhance androgen production and, for men, to decrease estrogen production. These include aromatase inhibitors, clomiphene, selective estrogen receptor modulators, and human chorionic gonadotropin. Other drugs used with the intention of improving athletic performance include human growth hormone, insulinlike growth factor 1, insulin, erythropoietin, stimulants, diuretics, levothyroxine, and gamma-hydroxybutyrate. Use of APEDs is increasing, with up to 5% of male and 2% of female college athletes using AASs and reports of a more than 20% usage rate among teenagers. Although many of these substances can increase muscle mass when combined with high levels of exercise and specific diets, it is not clear that they improve athletic performance. Furthermore, they are associated with a variety of serious adverse effects. AASs, in particular, can cause hepatotoxicity and acute cardiac events. Behavioral and psychiatric symptoms also can occur.

Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) syndrome associated with azithromycin presenting like septic shock: a case report.

INTRODUCTION: Drug reaction with eosinophilia and systemic symptoms syndrome is a potentially life-threatening cutaneous hypersensitivity reaction characterized by extensive mucocutaneous eruption, fever, hematologic abnormalities including eosinophilia and/or atypical lymphocytosis, and extensive organ involvement. The drugs most often responsible for causing drug reaction with eosinophilia and systemic symptoms syndrome are anticonvulsants, antimicrobial agents and antipyretic or anti-inflammatory analgesics. Although azithromycin is widely prescribed in clinical practice, serious cutaneous reactions from this agent have been rarely described. We report the first adult case of drug reaction with eosinophilia and systemic symptoms syndrome associated with azithromycin. CASE PRESENTATION: A 44-year-old previously healthy Caucasian man with history of tobacco use presented to his primary care physician with fever and productive cough. He was prescribed azithromycin, promethazine hydrochloride and dextromethorphan hydrobromide syrup. One week later, he developed a blistering erythematous rash over both hands, which over the next two weeks spread to involve nearly his entire body surface, sparing only his face. He was admitted to an outside hospital with signs of systemic inflammatory response syndrome and severe sepsis, presumably from a skin infection. Despite aggressive therapy he deteriorated, with worsening diffuse erythema, and was transferred to our institution. He developed multiple organ failure requiring ventilatory and hemodynamic support. Pertinent laboratory studies included a leukocytosis with a white blood cell count of 17.6 × 10(9)/L and 47% eosinophils. A skin biopsy showed evidence of spongiotic lichenoid dermatitis with eosinophils and neutrophils, compatible with a systemic drug-induced hypersensitivity reaction. Our patient was started on high-dose steroids and showed dramatic improvement within 48 hours. CONCLUSIONS: We report the first adult case of drug reaction with eosinophilia and systemic symptoms syndrome associated with azithromycin exposure. Clinicians should be aware of this potentially devastating complication from this commonly prescribed medication.

Is it prime time for alpha2-adrenocepter agonists in the treatment of withdrawal syndromes?

The need to treat withdrawal syndromes is a common occurrence in outpatient, inpatient ward, and intensive care unit (ICU) settings. A PubMed and Google Scholar search using alpha2-adrenoreceptor agonist (A2AA), specific A2AA agents, withdrawal syndrome and nicotine, and alcohol and opioid withdrawal terms was performed. A2AA agents appear to be able to modulate many of the signs and symptoms of significant withdrawal syndromes but are also capable of significant side effects, which can limit clinical use. Non-opioid oral A2AA agent use for opioid withdrawal has been well established. Pharmacologic combination therapy that utilizes A2AA agents for withdrawal syndromes appears promising but requires further formal testing to better define which other agents, under what condition(s), and at what A2AA doses are needed. The A2AA dexmedetomidine may be useful as an adjunctive agent in treating severe alcohol withdrawal syndromes in the ICU. In general, the current data does not support the routine use of A2AA as the primary or sole agent to treat ethanol/alcohol or nicotine withdrawal syndromes. Specific A2AA agents such as lofexidine has been shown to have a primary role in non-opioid-based treatment of opioid withdrawal syndrome and dexmedetomidine in combination with benzodiazepines has been shown to have potential in the treatment of severe ICU-based alcohol withdrawal syndrome.

Stimulants and the lung : review of literature.

Illicit stimulants, such as cocaine, amphetamine, and their derivatives (e.g., "ecstasy"), continue to exact heavy toll on health care in both developed and developing countries. The US Department of Health and Human Service reported over one million illicit drug-related emergency department visits in 2010, which was higher than any of the six previous years. Both inhaled and intravenous forms of these substances of abuse can result in a variety of acute and chronic injuries to practically every part of the respiratory tract, leading potentially to permanent morbidities as well as fatal consequences--including but not limited to nasal septum perforation, pulmonary hypertension, pneumothorax, pneumomediastinum, interstitial lung disease, alveolar hemorrhage, reactive airway disease, pulmonary edema, pulmonary granulomatosis, infections, foreign body aspiration, infections, bronchoconstriction, and thermal injuries. Stimulants are all rapidly absorbed substances that can also significantly alter the patient's systemic acid-base balance and central nervous system, thereby leading to further respiratory compromise. Mounting evidence in the past decade has demonstrated that adulterants coinhaled with these substances (e.g., levamisole) and the metabolites of these substances (e.g., cocaethylene) are associated with specific forms of systemic and respiratory complications as well. Recent studies have also demonstrated the effects of stimulants on autoimmune-mediated injuries of the respiratory tract, such as cocaine-induced midline destructive lesions. A persistent challenge to studies involving stimulant-associated respiratory toxidromes is the high prevalence of concomitant usage of various substances by drug abusers, including tobacco smoking. Now more than ever, health care providers must be familiar with the multitude of respiratory toxidromes as well as the diverse pathophysiology related to commonly abused stimulants to provide timely diagnosis and effective treatment.

Marijuana: respiratory tract effects.

Marijuana is the most commonly used drug of abuse in the USA. It is commonly abused through inhalation and therefore has effects on the lung that are similar to tobacco smoke, including increased cough, sputum production, hyperinflation, and upper lobe emphysematous changes. However, at this time, it does not appear that marijuana smoke contributes to the development of chronic obstructive pulmonary disease. Marijuana can have multiple physiologic effects such as tachycardia, peripheral vasodilatation, behavioral and emotional changes, and possible prolonged cognitive impairment. The carcinogenic effects of marijuana are unclear at this time. Studies are mixed on the ability of marijuana smoke to increase the risk for head and neck squamous cell carcinoma, lung cancer, prostate cancer, and cervical cancer. Some studies show that marijuana is protective for development of malignancy. Marijuana smoke has been shown to have an inhibitory effect on the immune system. Components of cannabis are under investigation as treatment for autoimmune diseases and malignancy. As marijuana becomes legalized in many states for medical and recreational use, other forms of tetrahydrocannabinol (THC) have been developed, such as food products and beverages. As most research on marijuana at this time has been on whole marijuana smoke, rather than THC, it is difficult to determine if the currently available data is applicable to these newer products.

The effects of opioids on the lung.

The term opioid refers to a broad class of medications that are used most frequently for their analgesic effects. Along with this effect, they also produce euphoria, and it is for this reason that they have been used illicitly, as well as medicinally, for thousands of years. While the most well-known complications of opioid use and misuse include respiratory and central nervous system depression, there are many other toxicities that have been associated with these drugs. Many complications can occur with multiple different opioids, such as non-cardiogenic pulmonary edema, while many of the complications are unique to the opioid used as well as the route of administration. This review focuses on the pulmonary complications associated with opioid use and abuse, but opioids can affect nearly every organ system. Their effects on the pulmonary system can be direct, such as causing granulomatous change, but they can also work indirectly. For example, opioids cause respiratory depression by decreasing sensitivity of peripheral chemoreceptors to carbon dioxide and decreasing activity in the central respiratory centers. Opioids have also been reported to affect the immune system, and place users at increased risk for many different infectious complications. Patients can have a wide array of signs and symptoms, sometimes making it difficult to recognize opioids as a cause for a patient's clinical picture. Due to the sedative effects of opioids, patients are also often not able to provide a reliable history. Knowledge of the possible toxicities of opioids can help prepare a physician to recognize the many complications associated with opioid use.

Pulmonary cystic disease associated with integumentary and renal manifestations.

A 69-year-old man with multiple skin lesions on his face, neck and upper torso, which first appeared in the 3rd decade of his life, was admitted to our hospital. He had cystic changes in his lungs noted on chest computed tomography (CT) scanning, as well as a left kidney mass. This patient exhibited a rare complex of renal, cutaneous and pulmonary manifestations, eponymously named Birt-Hogg-Dube syndrome, with characteristic skin features (fibrofolliculomas, trichodiscomas and acrochordons). This syndrome is due to an autosomal dominant germ-line mutation of the folliculin (FLCN) gene located at chromosome 17p11.2. Diagnosis and differentiation from other disease complexes including the skin, kidneys and lungs are important in prognostication and management of potentially life-threatening complications such as renal cell carcinoma and pneumothoraces.

Cerebral gas embolism in a case of Influenza A-associated acute respiratory distress syndrome treated with high-frequency oscillatory ventilation.

A 22-year-old obese asthmatic woman with Influenza A (H1N1)-associated acute respiratory distress syndrome died from cerebral artery gas emboli with massive cerebral infarction while being treated with High-Frequency Oscillatory Ventilation in the absence of a right to left intracardiac shunt. We review and briefly discuss other causes of systemic gas emboli (SGE). We review proposed mechanisms of SGE, their relation to our case, and how improved understanding of the risk factors may help prevent SGE in positive pressure ventilated patients.

The pharmacological approach to the elderly COPD patient.

The elderly patient (65 years and older) with chronic obstructive pulmonary disease (COPD) can be a challenge to the clinician. This begins with the correct and early diagnosis, the assessment of disease severity, recognizing complicating comorbidities, determining the burden of symptoms, and monitoring the frequency of acute exacerbations. Comprehensive management of COPD in the elderly patient should improve health-related quality of life, lung function, reduce exacerbations, and promote patient compliance with treatment plans. Only smoking cessation and oxygen therapy in COPD patients with hypoxemia reduce mortality. Bronchodilators, corticosteroids, methylxanthines, phosphodiesterase-4 inhibitors, macrolide antibiotics, mucolytics, and pulmonary rehabilitation improve some outcome measures such as spirometry measures and the frequency of COPD exacerbations without improving mortality. International treatment guidelines to reduce symptoms and reduce the risk of acute exacerbations exist. Relief of dyspnea and control of anxiety are important. The approach to each patient is best individualized. Earlier use of palliative care should be considered when traditional pharmacotherapy fails to achieve outcome measures and before consideration of end-of-life issues.