Severe asthma

Severe asthma is a term that is commonly used to describe patients with refractory, brittle, near fatal, and difficult-to-control asthma. Patients with severe asthma typically experience persistent symptoms despite medical therapy, report decreased quality of life and suffer an accelerated loss of lung function. The role of genetics, environmental exposure, and infection in the development of more severe asthma is the focus of ongoing research. While pathologic changes in these patients are now believed to involve lung parenchyma, in addition to large and small airways, the independent contribution of each of these compartments to the severe asthma phenotype is not well defined. The clinical evaluation of severe asthma patients should include investigating conditions commonly associated with severe asthma, such as gastroesophageal reflux disease, vocal cord dysfunction, and rhinosinusitis. In addition, advanced imaging techniques, measurement of exhaled gas or sputum indices, and airway biopsy are tools that may aid in evaluating severe asthma patients in the near future. Management of patients with severe asthma requires a comprehensive approach that includes non-pharmacological and pharmacological measures. Combination antiinflammatory and long-acting bronchodilator therapy remains the mainstay of management.     

Severe rhinosinusitis

Rhinosinusitis is diagnosed frequently in clinical practice, but the term may in fact encompass a wide spectrum of diseases. Inflammation of the nasal and sinus mucosa can arise from various causes and lead to different sequelae. Moreover, the term rhinosinusitis is more accurate than sinusitis. Causes range from a viral infection leading to the common cold to an invasive, fungal infection. An accurate diagnosis is important because effective therapy is available if recognized early and if specific therapy is used. Importantly, there is a close relationship between upper and lower airway disease and each have unique structural and functional differences that make an understanding of rhinosinusitis important not only for upper airway disease, but also for the management of asthma. All too often, rhinosinusitis becomes chronic and this becomes a challenge because medical therapy may not be sufficient to control disease. Finally, we should note that the differential diagnosis of rhinosinusitis is extensive and physicians should place heavy emphasis not only on the history, but also on appropriate imaging studies. A normal exam does not rule out the possibility or rhinosinusitis. Finally, we should emphasize that effective treatment is dependent on the etiology of the symptoms but also dependent on whether it is acute or chronic.     

Severe bronchiectasis

Bronchiectasis is primarily the result of airway injury and remodeling attributable to recurrent or chronic inflammation and infection. The underlying etiologies include autoimmune diseases, severe infections, genetic abnormalities, and acquired disorders. Recurrent airway inflammation and infection may also be the result of allergic or immunodeficiency states such as allergic bronchopulmonary mycoses or HIV/AIDS. Bronchiectasis should be included in the differentiation diagnosis of any patient with chronic respiratory complaints such as cough and sputum production. Early clinical manifestations may be subtle. Hallmarks of severe bronchiectasis include fetid breath, chronic cough, and sputum production. The associated chronic respiratory infections and airway sepsis are punctuated by episodes of acute exacerbation. Prompt recognition and treatment of bronchiectasis may allow for prevention of disease progression and irreversible loss of lung function. This review of severe non-cystic fibrosis bronchiectasis describes the current pathophysiology, clinical presentations, and management of bronchiectasis. We review how impaired airway clearance and the inability to resolve infection and inflammation creates a vicious cycle of recurrent injury. The common clinical features of bronchiectasis and findings are presented and illustrated by radiographic images. The common species and significance of various organisms often recovered from the distal airways including: tuberculous and environmental mycobacteria, aspergillus, and bacteria such as Pseudomonas aeruginosa will be covered. Management strategies including sputum surveillance, sputum clearance, antimicrobial therapy including antifungal and antimyobacterial agents as well as the evidence for the use of inhalational and anti-inflammatory therapies such as corticosteroids are also discussed. Recommendations for the work-up and therapy of complications including hemoptysis and respiratory failure are presented.     

Severe asthma: lessons from the Severe Asthma Research Program

Severe asthma affects only a small percentage of the asthma population. However, these patients remain poorly understood and difficult to treat. Because the numbers are relatively small (10% or less of the asthma population), a network approach with shared protocols, samples, and data provides a unique opportunity to recruit the numbers of subjects necessary to perform adequately powered studies. The Severe Asthma Network (Severe Asthma Research Program) was established by the National Heart, Lung, and Blood Institute in 2001 to advance collectively the study of severe asthma to determine factors that differentiated these patients or subjects from those with milder asthma. Nearly 800 subjects have been recruited in less than 4 years to begin to address these differences. Future studies will specifically evaluate the role of inflammatory/oxidative processes, infection, genetics, and the distal lung in the pathogenesis of severe asthma.     

Severe sepsis bundles

Sepsis is a complex syndrome with its wide spectrum of severity, and is one of the most common causes of death in Critical Care Units. The Surviving Sepsis campaign launched in 2004, is aimed at improving diagnosis, management and survival of patients with sepsis. Care bundles are a group of best evidence based interventions which when instituted together, gives maximum outcome benefit. Care Bundles are simple, uniform and have universal practical applicability. Surviving Sepsis campaign guidelines in 2008 incorporated two sepsis care bundles. The Resuscitation bundle includes seven key interventions to be achieved in 6-h while four interventions have to be completed within 24-h in the Management bundle. Compliance with a bundle implies achieving all the specified goals in that bundle. Limitations to care bundles include the quality of the evidence on which they are based, and that the relative contributions of each element of the bundle are not known. Several observational studies support the hypothesis that sepsis care bundles have an important role in improving outcomes from sepsis. Critical Care Units should develop management strategies to ensure compliance with the sepsis bundles in order to decrease hospital mortality due to severe sepsis.     

Severe acro-renal-uterine-mandibular syndrome

Although limb and renal defects occur together in a variety of patterns of multiple malformations, familial cases of acro-renal disorders are rare. In 1980, Halal et al. ?Am J Med Genet 5:277-284 described two sisters with unusual limb deficiencies, renal anomalies, and mandibular hypoplasia and termed this condition acro-renal-mandibular syndrome. A girl reported earlier by Fitch and Lachance ?1972; Can Med Assoc J 107:653-656 had similarly limb and renal findings, but an apparently normal jaw. We document three sibs with unusual limb deficiencies, renal agenesis, uterine anomalies in the two females, and orofacial defects, who clearly have a similar but more severe type of acrorenal disorder, apparently inherited as an autosomal recessive condition. The sibs with limb deficiencies and renal agenesis reported by Hennekam et al. ?1994; Am J Med Genet 53:102-107 appear to be additional cases of this very rare disorder, the pathogenesis of which may be related to abnormal epithelial-mesenchymal interactions.     

Severe bronchiolitis in children

Bronchiolitis is a common, acute, contagious lower respiratory tract illness of infants and young children. The majority of cases are secondary to respiratory syncytial virus. There are a number of risk factors for severe disease, including children less than six weeks of age and patients with atopy and/or asthma. The management requires vigilant monitoring and high-quality supportive care, including impressive use of fluids and nutritional support. Further research on anti-virals is essential to prevent respiratory syncytial virus induced bronchiolitis. Fortunately, the prognosis for the majority of normal infants who develop bronchiolitis is good.     

Severe Silver-Russell syndrome.

Three children are described with severe Silver-Russell syndrome. Major medical problems occurred in the first two years of life in all three. Silver-Russell syndrome should be considered in the differential diagnosis of children with severe pre- and postnatal growth deficiency.