This variability also poses major challenges to the study׳s execution. Immunodeficiency in AT is variable, with both humoral and cellular abnormalities. Translating the regulations and requirements as specified in the protocol into clinical conduct of the trial across all centers, countries, and regions represented another major challenge. Generally the causes of these diseases are unknown. General Information about Rare Lung Disease General Information about Rare Lung Disease Hermansky-Pudlak syndrome (HPS) is a rare multisystemic hereditary disease manifested by oculocutaneous albinism (OCA), visual impairment, and bleeding diathesis. IPF Advisory Board sponsored by Boehringer Ingelheim corporate. J.B.F. 1. On the basis of CT-measurements, loss of lung density is still to be observed even after the lung volume changes from progressive hyperinflation are eliminated [50,59] and, therefore, lung mass must reduce with emphysema progression. William E. Lawson, James E. Loyd, in Emery and Rimoin's Principles and Practice of Medical Genetics, 2013. Consequently, the practical alternative for use in routine clinical practice is that of physiological testing and the same approach has historically been adopted for the assessment of outcome in interventional studies of emphysema modifying therapy. 8-6), the differential diagnosis includes ossified amyloid deposits. For many years, whole-lung lavage remained the main therapeutic approach (154). EXACTLE generated similar results to the Dutch-Danish study that were also suggestive of a beneficial treatment effect on the rate of lung density decline. 10.7) but not on the imaging series acquired at functional residual capacity (FRC), or a combination of TLC and FRC imaging. Although BML is usually diagnosed after an incidental finding on chest imaging, patients can present with mild pulmonary symptoms such as dyspnea on exertion and cough. However, the practical difficulties of performing a randomized, placebo-controlled trial in a rare lung disease, such as AATD, using FEV1 as the outcome measure have been shown to be prohibitive [40]. Interstitial lung disease comes in more than 200 different types. Voxel distribution histograms. The 5-year mortality remains between 33% and 50% and is likely to vary based on the underlying disease process. Evaluations of these models delineated that macrophage function was impaired leading to the accumulation of foamy macrophages in the airspaces that were filled with surfactant-rich material, an observation identical to that seen in PAP. SFTPC mutations can not only cause ILD in childhood but have also been associated with pediatric cases of PAP (21). A1PI = α1 proteinase inhibitor. Consequently, where retardation of emphysema progression is the anticipated effect of antiproteolytic treatment, the optimal approach for reducing volume-related variability would appear to be the use of a statistical volume correction method to adjust lung density, measured from imaging acquired at full inspiration and expressed as a percentile index (as recommended by an expert working group [48] and currently employed in antitrypsin augmentation studies). Broncholaveolar lavage yields a milky opaque fluid rich in surfactant, while lung biopsy reveals eosinophilic material in the airspaces, but with relatively preserved alveolar architecture. This causes shortness of breath. *A1PI n = 92; placebo n = 85. The disease is not benign despite the hypothesis that BML originates from uterine leiomyomas, a common neoplasm that has a prevalence of 3–20%. While individual rare lung diseases affect less than 1 in 2000 individuals, collectively they have a significant impact upon the population at large. This relationship was interpreted as indicating the possible need for individually tailored dosing regimes, although future studies will be required to establish the validity of this supposition. Computed tomography reveals a pattern of ground glass opacification with intralobular and interlobular septal thickening. There are numerous possible causes of ILD, including connective tissue disorders, autoimmune diseases (e.g. Most cases are asymptomatic, and are most often diagnosed incidentally during intubation or bronchoscopy. The use of a treatment to promote structural repair, rather than to retard emphysema progression (as in AAT augmentation therapy), may influence the choice of methodological approach to reduce volume-related variability. Neuromuscular involvement, discoordinated swallowing, and impaired mucociliary clearance should be evaluated and managed, as for many patients susceptible to these disorders. Voxel distribution histograms in healthy and emphysematous lungs; the effect of lung density loss leads to a left shift in the histogram. Fig. Following the alarming first reports, pubic health concerns rapidly increased as AIDS was also diagnosed in other communities in the United States, in particular people who inject drugs, people with hemophilia and Haitian migrants; very soon AIDS had also been reported in many others countries and in every continent. Imaging-based morphometry has the additional advantage that a therapeutic response can be assessed within specified regions of the lung that would otherwise remain unidentified using global measures of lung function or localized tissue sampling. 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