A major genetic determinant of autoimmune diseases is associated with the presence of autoantibodies in hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis is an immune-mediated disease triggered by exposure to organic particles in susceptible individuals. It has been reported that a subgroup of patients with hypersensitivity pneumonitis develops autoantibodies with or without clinical manifestations of autoimmune disease. However, the mechanisms involved in this process and the effect of the autoantibodies on clinical course in hypersensitivity pneumonitis is unknown. We evaluated the association between human leukocyte antigen (HLA) class II alleles and hypersensitivity pneumonitis patients with and without autoantibodies. METHODS: 170 hypersensitivity pneumonitis patients were included. We analysed the presence of antinuclear antibodies, rheumatoid factor, anti-SSA/Ro, anti-SSB/La and anti-CCP at the time of diagnosis. In addition, in a subset of patients we evaluated anti-Scl-70, anti-neutrophil cytoplasmic antibody, and anti-DNA. HLA typing was performed using PCR sequence-specific primers in a high-resolution modality, including HLA-DRB1 and HLA-DQB1 loci. Statistical analysis was performed employing Epi-Info v7 and SPSS v20. RESULTS: 60 hypersensitivity pneumonitis patients showed sera autoantibodies (HPAbs+), and 110 hypersensitivity pneumonitis patients did not (HPAbs-). The frequency of the allele HLA-DRB1*03:01 was remarkably increased in the HPAbs+ group (10.8% versus 0.45%; OR 30.14, 95% CI 3.83-237.1; p=1.65×10-4 after Bonferroni's correction). Likewise, we found that the haplotype DRB1*03:01-DQB1*02:01, which is part of the 8.1 ancestral haplotype, a major genetic determinant of autoimmune diseases, confers significant risk to develop autoantibodies (OR 19.23, 95% CI 2.37-155.9; p=0.0088 after Bonferroni's correction). In addition, the HLA-DRB1*03:01 allele was associated with higher mortality in patients with hypersensitivity pneumonitis (adjusted OR 5.9, 95% CI 1.05-33.05; p=0.043). CONCLUSIONS: A subset of hypersensitivity pneumonitis patients presents circulating autoantibodies and higher mortality that are associated with some alleles of 8.1 ancestral haplotype.

Hemodynamic response to low-flow acute supplemental oxygen in idiopathic pulmonary fibrosis and elderly healthy subjects.

BACKGROUND: Hemodynamic response to supplemental oxygen in idiopathic pulmonary fibrosis (IPF) is still not well known. OBJECTIVE: To determine and compare the effect of low-flow acute supplemental oxygen on the hemodynamics of IPF patients and matched healthy subjects. METHODS: Descriptive and comparative study in 20 IPF-patients and 19 Control-subjects, (60-80 years old) breathing ambient air followed by acute nasal low-flow (3 L/min) supplemental oxygen. Non-invasive methods were used during the supine position to evaluate oxygen saturation, heart rate, stroke volume index, cardiac output index, total peripheral resistance and arterial blood pressure. RESULTS: Breathing ambient air, IPF (vs. Control) presented lower values in stroke volume index (38.7 [29.4-43.2] vs. 45.4 [38.4-50.9] mL•kg-1•m2; p=0.009) and cardiac output index (2.484 [2.268 - 2.946] vs. 2.857 [2.628 - 3.054] L•min-1•m-2; p=0.028), with higher total peripheral resistance (1644 [1559-2076] vs. 1505 [1366-1784] dyne•s•cm-5; p=0.017). During supplemental oxygen (vs. ambient air), both groups increased oxygen saturation above 94% (p<0.001) while heart rate decreased about 6 to 8% (p<0.001); stroke volume index increased around 7% in the Control-group (p=0.004) but only 1% in the IPF-group (p=0.017). In addition, IPF showed increments in total peripheral resistance (1644 [1559-2076] vs. 1706 [1554-2278] dyne•s•cm-5; p=0.017) with subsequent decrements in cardiac output index (2.484 [2.268 - 2.946] vs. 2.362 [2.139 - 2.664] L•min-1•m-2; p<0.001). CONCLUSION: Low-flow acute supplemental oxygen in IPF causes a meaningful decrement in cardiac output due to greater reduction in heart rate and increment in total peripheral resistance than matched healthy subjects. Knowing the hemodynamic profile of IPF patients may be helpful in determining their management with supplemental oxygen.