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Hot off the breath: triple therapy for idiopathic pulmonary fibrosis--hear the PANTHER roar

Idiopathic pulmonary fibrosis (IPF) is a disease characterised by alveolar epithelial damage followed by an aberrant repair mechanism characterised by fibroblast foci and activated myofibroblasts.1 Despite an incidence of 7.4/100 000 person years which is increasing year on year and a median survival of only 2–3 years, there is paucity of evidence for effective therapy.2 The current British Thoracic Society guidelines weakly recommend N-acetylcysteine (NAC), prednisolone and azathioprine (based on the IFIGENIA—Idiopathic Pulmonary Fibrosis International Group Exploring N-Acetylcysteine I Annual—trial) whereas the more recent guidelines of the American Thoracic Society/European Respiratory Society recommend lung transplantation or participation in a clinical trial as treatment options.3–5

 Increasing recognition of the clinical need for effective IPF therapy has finally led to a number of clinical trials evaluating potential anti-inflammatory and anti-fibrotic agents. IFIGENIA demonstrated that triple therapy with NAC, azathioprine and prednisolone was better...

Severity of Asthma Score Predicts Outcomes

Background:

The severity of asthma (SOA) score is based on a validated disease-specific questionnaire that addresses frequency of asthma symptoms, use of systemic corticosteroids, use of other asthma medications, and history of hospitalization/intubation for asthma. SOA does not require measurements of pulmonary function. This study compared the ability of SOA to predict clinical outcomes in the EXCELS (Epidemiological Study of Xolair [omalizumab]: Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate to Severe Asthma) patient population vs three other asthma assessment tools. EXCELS is a large, ongoing, observational study of patients with moderate to severe persistent asthma and reactivity to perennial aeroallergens.

 Methods:

Baseline scores for SOA, asthma control test (ACT), work productivity and impairment index-asthma (WPAI-A), and FEV1 % predicted were compared for their ability to predict five prespecified adverse clinical outcomes in asthma: serious adverse events (SAEs) reported as exacerbations, SAEs leading to hospitalizations, the incidence of unscheduled office visits, ED visits, and po or IV corticosteroid bursts related to asthma. Logistic regression analysis, area under receiver operating characteristic curves (AUCROCs), and classification and regression tree (CART) analysis were used to evaluate the ability of the four tools to predict adverse clinical outcomes using baseline and 1-year data from 2,878 patients enrolled in the non-omalizumab cohort of EXCELS.

 Results:

SOA was the only assessment tool contributing significantly in all five statistical models of adverse clinical outcomes by logistic regression analysis (full model AUCROC range, 0.689-0.783). SOA appeared to be a stand-alone predictor for four of five outcomes (reduced model AUCROC range, 0.689-0.773). CART analysis showed that SOA had the greatest variable importance for all five outcomes.

 Conclusions:

SOA score was a powerful predictor of adverse clinical outcomes in moderate to severe asthma, as evaluated by either logistic regression analysis or CART analysis.

 Trial registry:

ClinicalTrials.gov; No.: NCT00252135; URL: www.clinicaltrials.gov

Risk Factors and Mycobacterium avium Complex

Background:

The cause of observed increases in pulmonary Mycobacterium avium complex (pMAC) isolation and disease is unexplained. To explore possible causes of the increase in pMAC isolation and disease prevalence in Ontario, Canada, we studied age and other population-level risk factors.

 Methods:

We determined age and sex of patients with pMAC disease between 2003 and 2008. We then estimated whether the potential effect of population aging and changes in prevalence of HIV infection, solid organ transplant, COPD, and tumor necrosis factor-α (TNF-α) inhibition have contributed to the observed increase in pMAC disease.

 Results:

During 2003 to 2008, pMAC isolation and disease prevalence (per 100,000) both increased (8.44 to 12.62 and 4.35 to 6.81, respectively). The total number of cases of disease increased by 348 (2.46 per 100,000). Based on actual contemporary population changes, aging could explain 70 additional cases (increase of 0.57 per 100,000). The increase in self-reported COPD prevalence could potentially explain 11 (95% CI, 0-42) additional cases (increase of 0.09 per 100,000 [95% CI, 0-0.34 per 100,000]). HIV infection, solid organ transplant, and TNF-α inhibition combined could potentially explain no more than 73 additional cases (increase of 0.60 per 100,000).

 Conclusions:

Although population aging appears to be a major risk factor, the increase in pMAC disease in Ontario could be only partly explained by aging, increases in COPD, HIV, solid organ transplantation, and TNF-α inhibition therapy. The increase in pMAC is likely multifactorial and may be affected by environmental or pathogen factors not addressed in this study.

Imaging in pulmonary hypertension, part 3: small vessel diseases

Pulmonary hypertension is a significant cause of morbidity and mortality. Unfortunately, non-specific presentation and lack of awareness of the disease frequently lead to significant delay in diagnosis, often with the onset of right heart failure, when prognosis is poor and therapy is of limited effectiveness.

The classification of pulmonary hypertension is a clinical one grouping diseases into categories with similar patho-physiological mechanism and therapeutic options. Pulmonary biopsy can provide a definitive diagnosis but is hazardous in patients with pulmonary hypertension. Imaging has emerged as an invaluable tool in differentiating the aetiology, assessing disease severity and directing further management. One of the most important roles of imaging is to differentiate diseases resulting from obstruction of the large pulmonary arteries from those secondary to diffuse small vessel disease, as these have very different prognosis and are also treated differently. Small vessel diseases causing pulmonary arterial hypertension most commonly result from diffuse remodelling of the pulmonary arterioles. There are multiple causes of arteriolar remodelling which share similar histopathological, clinical and imaging features. In a subgroup of small vessel diseases causing pulmonary hypertension the predominant site of increased vascular resistance is at the level of the capillaries or venules.

Correct diagnosis of pulmonary veno-occlusive disease and pulmonary capillary haemangiomatosis is essential since poor prognosis and inadvertent administration of vasodilators (conventional therapy for arteriolar predominant disease) can result in fatal pulmonary oedema. Multimodality imaging plays an important role in suggesting a diagnosis, guiding further investigation and directing treatment.

Imaging in pulmonary hypertension, part 1: clinical perspectives, classification, imaging techniques and imaging algorithm

Pulmonary arterial hypertension (PAH) is an uncommon condition associated with significant morbidity and mortality. It has diverse aetiology with differing clinical presentations, imaging features and treatments that range from surgical treatment of proximal chronic thromboembolic disease to targeted medical therapies in small vessel disease. Current classification of pulmonary hypertension (PH) is clinically based and groups diseases with similar pathophysiological mechanisms and therapeutic approaches.

Groupings include conditions characterised by diffuse small vessel diseases such as idiopathic PAH, PH secondary to chronic hypoxic lung disease, left sided cardiac disease, chronic large vessel obstruction such as chronic thromboembolic disease and a miscellaneous group of diseases. The physiological manifestation of all of these diseases is increased pulmonary vascular resistance and PAH and while clinical features may provide a clue to diagnosis imaging plays a fundamental role in establishing a precise diagnosis and therefore guides therapy. A broad range of imaging modalities is available for the patient with suspected PH including chest radiograph, echocardiography, ventilation/perfusion scintigraphy, catheter pulmonary angiography as well as cross-sectional CT and MRI. Each modality has its strengths and limitations and different techniques may be used at different stages of diagnostic investigation and frequently complement each other. For example, while MRI and echocardiography permit cardiac structural and functional assessment, CT pulmonary angiography provides exquisite morphological information about the proximal pulmonary vasculature and lung parenchyma but little functional information. Modern cross-sectional imaging techniques (CT and MRI) hold the promise of a comprehensive evaluation of the heart, circulation and lung parenchyma in PH.

The authors present a multimodality-imaging algorithm for the investigation of patients with suspected PH though it is acknowledged that there is some variation in practice depending on availability of resources and expertise.

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