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Thoracic Diseases Associated with HIV Infection in the Era of Antiretroviral Therapy: Clinical and Imaging Findings.

The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) pandemic has entered its 4th decade. Since the introduction of combination antiretroviral therapy (ART) in 1996, the number of AIDS-related deaths has plateaued worldwide. Today, owing to the effectiveness of ART, the HIV-infected population is aging and HIV infection has become a chronic illness.

Non-AIDS comorbidities are increasing, and the spectrum of HIV-related thoracic diseases is evolving. In developed countries, bacterial pneumonia has become more common than Pneumocystis pneumonia. Its imaging appearance depends on the responsible organism, most commonly Streptococcus pneumoniae. Mycobacterium tuberculosis continues to be a major threat. Its imaging patterns vary depending on CD4 count.

Primary lung cancer and Hodgkin lymphoma are two important non-AIDS-defining malignancies that are increasingly encountered at chest imaging. Human herpesvirus 8, also known as Kaposi sarcoma-associated herpesvirus (KSHV), is strongly linked to HIV-related diseases, including Kaposi sarcoma, multicentric Castleman disease, KSHV inflammatory cytokine syndrome, and primary effusion lymphoma. Immune reconstitution inflammatory syndrome is a direct complication of ART whose manifestations vary with the underlying disease. Given the high rate of smoking among HIV-infected patients, chronic obstructive pulmonary disease is another important cause of morbidity and mortality. A high degree of suspicion is required for the early diagnosis of pulmonary arterial hypertension and lymphocytic interstitial pneumonia, given their nonspecific manifestations.

Finally, multilocular thymic cyst manifests as a cystic anterior mediastinal mass. Recognition of the clinical and radiologic manifestations of these less traditional HIV-related diseases can expedite diagnosis and treatment in the ART era. © RSNA, 2014.

Secondary Bacterial Infections in Influenza Virus Infection Pathogenesis.

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BacteriaInfluenza is often complicated by bacterial pathogens that colonize the nasopharynx and invade the middle ear and/or lung epithelium. Incidence and pathogenicity of influenza-bacterial coinfections are multifactorial processes that involve various pathogenic virulence factors and host responses with distinct site- and strain-specific differences.

Animal modelsAnimal models and kinetic models have improved our understanding of how influenza viruses interact with their bacterial co-pathogens and the accompanying immune responses. Data from these models indicate that considerable alterations in epithelial surfaces and aberrant immune responses lead to severe inflammation, a key driver of bacterial acquisition and infection severity following influenza. However, further experimental and analytical studies are essential to determining the full mechanistic spectrum of different viral and bacterial strains and species and to finding new ways to prevent and treat influenza-associated bacterial coinfections.

Here, we review recent advances regarding transmission and disease potential of influenza-associated bacterial infections and discuss the current gaps in knowledge.

Hospitalized patients with COPD: analysis of prior treatment.

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Objective: Although COPD is a prevalent disease, it is undertreated, and there are no available data regarding previous treatment of COPD in Brazil. This study aimed to determine the appropriateness of maintenance treatment in COPD patients prior to their hospitalization and to identify variables associated with inappropriate treatment.

Methods: This was an observational, cross-sectional, analytical study involving 50 inpatients with COPD at two hospitals in the city of Florianópolis, Brazil. The patients completed a questionnaire on parameters related to the maintenance treatment of COPD. Non-pharmacological management and pharmacological treatment were assessed based on the recommendations made by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) in 2011 and by the Brazilian National Ministry of Health in the chronic respiratory diseases section of its Caderno de Atenção Básica (CAB, Primary Care Guidebook).

Results: In most of the patients, the COPD was classified as being severe or very severe. Regarding non-pharmacological management, 33% of the patients were smokers, only 32% had been advised to receive the flu vaccine, 28% had received pneumococcal vaccine, and only 6.5% of the patients in the B, C, and D categories received pulmonary rehabilitation. Regarding GOLD and CAB recommendations, pharmacological treatment was inappropriate in 50% and 74% of the patients, respectively. Based on GOLD recommendations, 38% were undertreated. A low level of education, low income, not receiving oxygen therapy, and not receiving the flu vaccine were associated with inappropriate treatment.

Conclusions: The application of various non-pharmacological management recommendations was unsatisfactory. Regarding the GOLD recommendations, the high rate of inappropriate maintenance treatment was mainly due to undertreatment. In Brazil, even in severe COPD cases, optimizing treatment to achieve greater benefits continues to be a challenge.

Inhaled Dry Powder Formulations for Treating Tuberculosis.

Tuberculosis is the second leading cause of death from infectious diseases. Although anti-tubercular drugs have been traditionally administered orally, there is a growing interest in delivering drugs via the pulmonary route using nebulisers or dry powder inhalers. Drugs in dry powder inhalers (DPI) are stable and DPI are user-friendly compared to nebulisation which is time consuming, inconvenient and inefficient and requires special equipment.

For tuberculosis treatment, drugs should target alveolar macrophages that harbour microorganisms and/or maintain high drug concentration at the infection site in the lung. Drug particles include micro-particles or nanoparticles. Powders can be engineered by micronisation, crystallisation, spray drying, freeze drying and particle coating approaches. The formulation may contain single or combination drugs.

This paper will provide an update on current status of TB, its pathogenesis, current treatment strategies, shortcomings of current oral or parenteral delivery strategies, pulmonary delivery devices, advantages of pulmonary delivery of powder formulations, formulation approaches and pharmacokinetic studies of pulmonary delivery of powders for inhalation.

Is there a rationale and role for long-acting anticholinergic bronchodilators in asthma?

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Despite current guidelines and the range of available treatments, over a half of patients with asthma continue to suffer from poor symptomatic control and remain at risk of future worsening. Although a number of non-pharmacological measures are crucial for good clinical management of asthma, new therapeutic controller medications will have a role in the future management of the disease.

Several long-acting anticholinergic bronchodilators are under investigation or are available for the treatment of respiratory diseases, including tiotropium bromide, aclidinium bromide, glycopyrronium bromide, glycopyrrolate and umeclidinium bromide, although none is yet licensed for the treatment of asthma. A recent Phase III investigation demonstrated that the once-daily long-acting anticholinergic bronchodilator tiotropium bromide improves lung function and reduces the risk of exacerbation in patients with symptomatic asthma, despite the use of inhaled corticosteroids (ICS) and long-acting β2-agonists (LABAs). This has prompted the question of what the rationale is for long-acting anticholinergic bronchodilators in asthma. Bronchial smooth muscle contraction is the primary cause of reversible airway narrowing in asthma, and the baseline level of contraction is predominantly set by the level of 'cholinergic tone'. Patients with asthma have increased bronchial smooth muscle tone and mucus hypersecretion, possibly as a result of elevated cholinergic activity, which anticholinergic compounds are known to reduce.

Further, anticholinergic compounds may also have anti-inflammatory properties. Thus, evidence suggests that long-acting anticholinergic bronchodilators might offer benefits for the maintenance of asthma control, such as in patients failing to gain control on ICS and a LABA, or those with frequent exacerbations.

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