Clinical Phenotypic Analysis Of Connective Tissue-associated Interstitial Pulmonary Disease

Objective:Connective tissue disease(CTD)includes: Systemic lupus erythematosus(SLE),Rheumatoid arthritis(RA),Systemic sclerosis(SSc),Sjogren ’s syndrome(SS),Polymyositis/Dermatomyositis(PM/DM),etc.Although different types of connective tissue diseases can cause Interstitial pulmonary disease(ILD),However,the imaging features,clinical manifestations and prognosis of different types of Connective tissue disease-interstitial pulmonary disease(CTD-ILD)are different.Therefore,the clinical phenotypic analysis of connective tissue associated interstitial pulmonary disease is particularly important.At present,there is no clear diagnostic criteria for CTD-ILD.This study aims to provide reference for diagnosis and treatment by analyzing different clinical manifestations of CTD-ILD phenotypes,auxiliary examinations and risk factors.Methods:1.General information,clinical manifestations and laboratory tests of patients first diagnosed with connective tissue disease from 2009 to 2020 were collected.2.According to the presence or absence of interstitial lung,the patients weredivided into two groups: group with interstitial lung and group withoutinterstitial lung.3.The general conditions,clinical manifestations and laboratory examinationsof different connective tissue diseases with interstitial lung and withoutinterstitial lung were compared.4.Logistic binary regression was used to analyze the risk factors of interstitial pneumonia in different connective tissue diseases.Results:1.The mean age of SS group with interstitial lung was higher than that of the group without interstitial lung((49)<0.05).In the first symptoms,respiratory symptoms were more common in the group with interstitial lung than in the group without interstitial lung((49)<0.05).Chest CT/HRCT of interstitial lung in Sjogren’s syndrome was mostly patchy.In laboratory tests,the levels of white blood cell count,lactate dehydrogenase and triglyceride in the patients with interstitial lung were higher than those in the patients without interstitial lung((49)<0.05),and the levels of high-density lipoprotein were lower than those in the patients without interstitial lung((49)<0.05).The number of positive cases of ribosomal U1 RNP antibody and anti-mitochondrial M2 antibody in Sjogren’s syndrome combined with interstitial lung group was lower than that in Sjogren’s syndrome combined with interstitial lung group((49)<0.05),and the number of positive cases of JO-1 antibody was higher than that in the uncombined interstitial lung group((49)<0.05).Old age(≥60 years old)(OR=5.541,95%CI: 1.409-21.797)and reduced HDL(OR=8.192,95%CI:1.065-63.004)were risk factors for the development of interstitial lung in Sjogren’s syndrome.2.The age of onset of PM/DM patients with interstitial pulmonary disease group was higher than that of the group without interstitial pulmonary disease((49)<0.05).In the first symptoms,rash was more common in both the patients with interstitial lung and those without interstitial lung((49)<0.05).Compared with the group without interstitial lung,respiratory symptoms were more common in the group with interstitial lung((49)<0.05),muscle weakness was less common in 18 cases(46.7%)and rash was less common in 26 cases(66.7%)than in the group without interstitial lung((49)<0.05).Myositis/Dermatomyositis combined with interstitial lung chest HRCT/CT was most common in patches(29 cases,40.8%).In laboratory tests,C-reactive protein,glutamyltranspeptidase,serum globulin and Ig M were higher in patients with interstitial lung than those without interstitial lung((49)<0.05),and serum albumin levels were lower in patients with interstitial lung than those without interstitial lung((49)<0.05).Among the autoimmune antibodies,52 k D protein positive was the most common in both the interstitial lung group and the uninterstitial lung group((49)<0.05).Elevated CRP(OR=1.187,95%CI: 1.052-1.338)was an independent risk factor for myositis/dermatomyositis with interstitial pneumonia.3.The age of onset of RA patients with interstitial pulmonary disease was higher than that of the group without interstitial pulmonary disease((49)<0.05).In the first symptoms,joint pain was more common in the patients with interstitial lung and those without interstitial lung((49)<0.05).Dyspnea,general fatigue,cough,sputum,edema and fever were more common in the group with interstitial lung than in the group without interstitial lung((49)<0.05),and morning stiffness was less common than in the group without interstitial lung((49)<0.05).Chest HRCT/CT demonstrates rheumatoid arthritis with interstitial pulmonary changes with patchy lesions predominating.WBC,LDH,tropoprotein,PCT,λ light chain,C4,CA50,cytokeratin19 fragment,anti-O,CA125,squamous SSC in rheumatoid arthritis with interstitial lung group were higher than those in rheumatoid arthritis without interstitial lung group((49)<0.05).Serum total protein,albumin,white bulb ratio and rheumatoid factor were lower than those in rheumatoid arthritis group without interstitial lung((49)<0.05).52 k D protein positive was the most common in patients with and without interstitial lung((49)>0.05).The positive rates of SSA antibody and hiprotein antibody in patients with Sjogren’s syndrome were higher in patients with interstitial lung than those without interstitial lung((49)<0.05),while the positive rates of Smith antibody,anti-mitochondrial M2 antibody,ribosomal P protein antibody and anti-proliferative nuclear antibody were lower in patients with interstitial lung than those without interstitial lung((49)<0.05).Increased levels of anti-O(OR=1.070,95%CI: 1.002-1.142)and cytokeratin 19 fragment(OR=21947.218,95%CI:6.139-78461528.392)were risk factors for interstitial pneumonia in rheumatoid arthritis.4.The mean age of SLE with interstitial lung was higher than that of the group without interstitial lung((49)>0.05).Among the first symptoms,joint pain was more common in the group with interstitial lung((49)<0.05),and rash was more common in the group without interstitial lung((49)<0.05).Arthritis pain,cough,expectoration and dyspnea were more common in the group with interstitial lung than in the group without interstitial lung((49)<0.05),and rash and edema were less common in the group with interstitial lung than in the group without interstitial lung((49)<0.05).Chest HRCT/CT showed patchy opacities(92.9% of 52 cases).Laboratory examination showed that the hemoglobin,albumin,CEA,HCT,CRP,AFP,CA153,neuron-specific enolase,hospitalization times and β2 microglobulin were higher in the group with interstitial lung than in the group without interstitial lung((49)<0.05).LDL,ALB,HDL and Ig A were lower than those in SLE group without interstitial lung((49)<0.05).Among autoimmune antibodies,the positive rates of JO-1 antibody and anti-double-stranded DNA antibody in the combined interstitial lung group were lower than those in the uncombined interstitial lung group((49)<0.05).High GP,high CRP,low ALB,,high CA153 and high β2 microglobulin were the risk factors of interstitial pneumonia.5.There was no significant difference in the age of onset between the patients with SSc complicated with interstitial lung and those without.Among the first symptoms,fever,Raynold’s phenomenon,joint swelling and pain were more common in the group with interstitial lung than in the group without interstitial lung((49)<0.05),while rash and sclerosis of the skin were less common in the group with interstitial lung than in the group without interstitial lung((49)<0.05).Chest HRCT/CT showed systemic sclerosis with interstitial lung with patchy and cystic shadows most frequently.The lymphocyte count in patients with interstitial lung was higher than that in patients with systemic sclerosis without interstitial lung((49)<0.05),and the serum total protein and serum albumin were lower than those in patients with systemic sclerosis without interstitial lung((49)<0.05).Among the autoimmune antibodies,scleroderma 70 antibody positive was the most common in patients with and without interstitial lung((49)>0.05).Conclusion:1.Patients with different types of CTD combined with interstitial lung have different clinical manifestations,laboratory examination and imaging manifestations.2.In patients with the same type of CTD,there were differences in clinical manifestations,laboratory examinations and other auxiliary examinations between the patients with interstitial lung and those without interstitial lung.3.Risk factors of ILD are different in patients with different CTD.Older age(≥60years old)and reduced HDL are risk factors for interstitial pneumonia in patients with Sjogren’s syndrome.High CRP level is an independent risk factor for interstitial pneumonia in patients with myositis/dermatomyositis.High GP,high CRP,low ALB,high CA153 and high β2 microglobulin are the risk factors of interstitial pneumonia in SLE patients.High levels of anti-O and cytokeratin 19 fragments are risk factors for interstitial pneumonia in patients with rheumatoid arthritis.