Donor Surfactant Protein A2 Polymorphism and Lung Transplant Survival.

Purpose Gene polymorphisms of surfactant proteins, key players in lung innate immunity, have been associated with various lung diseases. The aim of this study was to investigate the potential association between variations within the SP-A gene of the donor lung allograft and recipient post-transplant outcome. Methods Lung-Tx pts (n=192) were prospectively followed by PFTs, bronchoscopies with BAL and biopsies. Donor lungs were assayed for SP-A1 (6An) and SP-A2 (1An) gene polymorphism by using the pyrosequencing method. Unadjusted and adjusted stratified Cox survival models are reported. Results SP-A1 and SP-A2 genotype frequency and lung transplant recipient and donor characteristics as well as the cause of death are noted. Recipients were grouped per donor SP-A2 variants. Individuals that received lungs from donors with the SP-A2 1A0 (n=102) versus 1A1 variant (n=68) or SPA2 genotype 1A01A0 (n=54) versus 1A0A1 (n=38) had greater survival at one year (logrank p<0.025). No significant association was noted for SP-A1 variants. Stratified adjusted survival models for one year survival and diagnosis showed a reduced survival for 1A1 variant and the 1A01A1 genotype. Furthermore, when survival was conditional on one year survival no significance was observed, indicating that the survival difference were due to the first year's outcome associated with the 1A1 variant. Conclusion Donor lung SP-A gene polymorphisms are associated with post-transplant clinical outcome. Lungs from donors with the SP-A2 variant 1A1 had a reduced survival at one year. The observed donor genetic differences, via innate immunity relate to the post-transplant clinical outcome.PURPOSE: Gene polymorphisms of surfactant proteins, key players in lung innate immunity, have been associated with various lung diseases. The aim of this study was to investigate the potential association between variations within the SP-A gene of the donor lung allograft and recipient post-transplant outcome. METHODS: Lung-Tx pts (n=192) were prospectively followed by PFTs, bronchoscopies with BAL and biopsies. Donor lungs were assayed for SP-A1 (6An) and SP-A2 (1An) gene polymorphism by using the pyrosequencing method. Unadjusted and adjusted stratified Cox survival models are reported. RESULTS: SP-A1 and SP-A2 genotype frequency and lung transplant recipient and donor characteristics as well as the cause of death are noted. Recipients were grouped per donor SP-A2 variants. Individuals that received lungs from donors with the SP-A2 1A0 (n=102) versus 1A1 variant (n=68) or SPA2 genotype 1A01A0 (n=54) versus 1A0A1 (n=38) had greater survival at one year (logrank p<0.025). No significant association was noted for SP-A1 variants. Stratified adjusted survival models for one year survival and diagnosis showed a reduced survival for 1A1 variant and the 1A01A1 genotype. Furthermore, when survival was conditional on one year survival no significance was observed, indicating that the survival difference were due to the first year's outcome associated with the 1A1 variant. CONCLUSION: Donor lung SP-A gene polymorphisms are associated with post-transplant clinical outcome. Lungs from donors with the SP-A2 variant 1A1 had a reduced survival at one year. The observed donor genetic differences, via innate immunity relate to the post-transplant clinical outcome

Association of surfactant protein A polymorphisms with otitis media in infants at risk for asthma

BACKGROUND: Otitis media is one of the most common infections of early childhood. Surfactant protein A functions as part of the innate immune response, which plays an important role in preventing infections early in life. This prospective study utilized a candidate gene approach to evaluate the association between polymorphisms in loci encoding SP-A and risk of otitis media during the first year of life among a cohort of infants at risk for developing asthma. METHODS: Between September 1996 and December 1998, women were invited to participate if they had at least one other child with physician-diagnosed asthma. Each mother was given a standardized questionnaire within 4 months of her infant's birth. Infant respiratory symptoms were collected during quarterly telephone interviews at 6, 9 and 12 months of age. Genotyping was done on 355 infants for whom whole blood and complete otitis media data were available. RESULTS: Polymorphisms at codons 19, 62, and 133 in SP-A1, and 223 in SP-A2 were associated with race/ethnicity. In logistic regression models incorporating estimates of uncertainty in haplotype assignment, the 6A(4)/1A(5)haplotype was protective for otitis media among white infants in our study population (OR 0.23; 95% CI 0.07,0.73). CONCLUSION: These results indicate that polymorphisms within SP-A loci may be associated with otitis media in white infants. Larger confirmatory studies in all ethnic groups are warranted

Surfactant protein A and B genetic variants predispose to idiopathic pulmonary fibrosis

Derangement in pulmonary surfactant or its components and alveolar collapse are common findings in idiopathic pulmonary fibrosis (IPF). Surfactant proteins play important roles in innate host defense and normal function of the lung. We examined associations between IPF and genetic polymorphic variants of surfactant proteins, SP-A1, SP-A2, SP-B, SP-C, and SP-D. One SP-A1 (6A(4)) allele and single nucleotide polymorphisms (SNPs) that characterize the 6A(4) allele, and one SP-B (B1580_C) were found with higher frequency (Pless than or equal to0.01) in nonsmoker and smoker IPF (n=84) subgroups, respectively, compared with healthy controls (n=194). To explore whether a tryptophan (present in 6A(4)) or an arginine (present in other SP-A1 alleles and in all SP-A2 alleles) at amino acid 219 alters protein behavior, two truncated proteins that varied only at amino acid 219 were oxidized by exposure to ozone. Differences in the absorption spectra (310-350 nm) between the two truncated recombinant SP-A proteins were observed both before and after protein oxidation, suggesting allele-specific aggregation differences attributable to amino acid 219. The SP-B SNP B1580_C (odds ratio:7.6

Clinical results and development of heterotopic ossification in total cervical disc replacement during a 4-year follow-up

Cervical total disc replacement (CTDR) aims to decrease the incidence of adjacent segment disease through motion preservation in the operated disc space. Ongoing data collection and increasing number of studies describing heterotopic ossification (HO) resulting in decreased mobility of implants, forced us to carefully evaluate our long-term clinical and morphological results of patients with CTDR. We present the first 54 consecutive patients treated with 65 ProdiscC™ prostheses during a 12-month period (2/2004–3/2005). All patients signed an informed consent and were included in prospective long-term study approved by hospital ethical committee. The 1- and 2-year follow-up analysis were available for all patients included and 4-year results for 50 patients (60 implants). Clinical (neck disability index-NDI, visual analog scale-VAS) and radiological follow-up was conducted at 1-, 2- and 4-years after the procedure. The Mehren/Suchomel modification of McAfee scale was used to classify the appearance of HO. Mean preoperative NDI was 34.5%, VAS for neck pain intensity 4.6 and VAS for arm pain intensity 5.0. At 1-, 2- and 4-year follow-up, the mean NDI was 30.7, 27.2, and 30.4, mean VAS for neck pain intensity 2.5, 2.1 and 2.9 and mean VAS for arm pain intensity pain 2.2, 1.9 and 2.3, respectively. Significant HO (grade III) was present in 45% of implants and segmental ankylosis (grade IV) in another 18% 4 years after intervention. This finding had no clinical consequences and 92% of patients would undergo the same surgery again. Our clinical results (NDI, VAS) are comparable with fusion techniques. Although, advanced non-fusion technology is used, a significant frequency of HO formation and spontaneous fusion in cervical disc replacement surgery must be anticipated during long-term follow-up