Analysis Of Clinical Features And Cough Characteristics Of Patients With Interstitial Lung Disease

BackgroundIdiopathic interstitial pneumonia(IIP),interstitial pneumonia with autoimmune features(IPAF),and connective tissue disease associated interstitial lung disease(CTDILD)are important components of interstitial lung disease(ILD).They have similar imaging and histopathological classifications,lung function is manifested as restrictive ventilation dysfunction and decreased diffusion function,as while as PaO2 declines during exercise.ILD commonly manifest as exertional dyspnea and cough,but these symptoms are nonspecific and lead to a high probability of misdiagnosis.Limulus liquefaction sugar chain antigen(KL-6)is a glycoprotein on the membrane of type II alveolar epithelial cells,which is mainly secreted by proliferating,regenerative,or impaired alveolar type II epithelial cells and can be shed from type II alveolar epithelial cells into the alveolar space and blood.It is currently considered to be the most promising biomarker for ILD diagnosis,contributes to the diagnosis and acute exacerbation of ILD.The sugar chain antigen 19-9(CA19-9)is produced by respiratory bronchiolar epithelial cells,may play a role in lung injury in patients with pulmonary fibrosis.A significant increase in serum KL-6 and CA19-9 is one of the factors that have a poor prognosis in patients with pulmonary fibrosis.According to the imaging and/or pathological features,in addition to diffuse alveolar damage(DAD),compared with other non-ordinary interstitial pneumonia(UIP)types,patients with UIP have poor treatment and prognosis.Clinically,ILD patients which have increased airway pressure,worsened lung function,increased chest imaging lesions suggest worsening of the disease.Since ILD is not common in clinical practice,it is difficult for most physicians to understand its clinical,imaging and pathological characteristics.We first differentiated between UIP and non-UIP by analyzing their imaging and pathological characteristics and then compared the patients' symptoms,pulmonary function tests and serum indicators.Our study may help clinicians better evaluate the progression and prognosis of UIP and non-UIP using common tests.There is no research for similar grouping and clinical characteristics analysis.Cough is one of the most important clinical symptoms of ILD in some types of ILD such as idiopathic pulmonary fibrosis(IPF),sarcoidosis,chronic allergic alveolitis(HP),and systemic sclerosis.Patients with SSc-ILD have a very high cough frequency,while IPF patients have the most severe cough degree.However,the mechanisms underlying ILD-associated cough remain unclear.Related studies suggest that it is associated with pulmonary structural malformation and intensification of mechanical stimulus,impairment of cough inhibitory nerves,increasing cough sensitization,overexpression of neurotrophic factors,hyperfunction of sensory neuron,overproduction of airway mucus and nonpulmonary comorbidities.The studies of IPF have demonstrated cough as an independent risk factor of disease progression which is useful for evaluating the patient's mortality and time to lung transplantation.Moreover,the clinical diagnosis of ILD-related cough must be made after definite ILD diagnosis.The characteristics of cough in ILD patients and their significance in the development of ILD are not clear.Objectives1.To compare the clinical characteristics,pulmonary function tests and serum indicators between patients with UIP and non-UIP,and to investigate the factors affecting the prognosis of patients with interstitial lung diseases.2.To analyze the clinical characteristics of cough in patients with interstitial lung diseases,including IIP,CTD-ILD and IPAF,further providing clinical evidence for treating cough associated with interstitial lung diseases.Methods1.A total of 107 in patients with interstitial lung diseases were enrolled in the Respiratory Department of The First Affiliated Hospital of Guangzhou Medical University,from October 2016 to October 2017.They were divided into either UIP group or non-UIP group according to the results of lung biopsy and/or high resolution computed tomography.We compared the basic patient information,clinical symptoms,pulmonary function tests and serum indicators between the two groups,and followed up the patients by phone in March 2018,The follow-up including symptom assessment,treatment,and changes in patients' conditions.Study endpoint was worsening or death due to interstitial lung diseases.Whether the endpoint occurred,the patients were divided into either worsening group or stable group to investigate the factors affecting the prognosis of patients with interstitial lung diseases.2.According to cough frequency,all patients were divided into either group A(patients with multiple coughs per day which often affect the daily activities)or group B(patients with infrequent coughs which are intermittent,transient and unpredictable or patients without coughs).The basic characteristics,pulmonary function tests,serum indicators and outcomes were compared between the two groups.3.According to visual analogue scale(VAS)score,all patients were divided into either high-VAS-score group(at least 5 points)or low-VAS-score group(less than 5 points),and their pulmonary function tests and laboratory tests were compared.4.Statistical methods: SPSS 17.0 statistical software was used for data analysis,and chi-square test was used for counting data.The normal distribution data were represented by mean plus or minus standard deviation(x±s),and t test was used.The data of skewness distribution are represented by median and quartile spacing.Logistic regression was used for multivariate analysis.P < 0.05 indicates that the difference is statistically significant.Results1.Comparative analysis of clinical characteristics between UIP and non-UIP patients1).131 patients with ILDs were surveyed at the Repiratory Department of the First Affiliated Hospital of Guangzhou Medical University,from October 2016 to October 2017.A total of 107 eligible patients were enrolled,including 25 in UIP group and 82 in non-UIP group.The ratio of male to female between UIP group and non-UIP group was 2.5:1 and 1:1.3,The mean age was significantly higher in UIP group than nonUIP group(60.28±8.96 vs.53.74±12.97).respectively(P<0.05).UIP group had more smokers than non-UIP group(P=0.003).2).Most patients in both UIP group and non-UIP group showed shortness of breath(80% vs.87.8%),cough(92% vs.81.7%),expectoration(24% vs.29.3%),and Velcro crackles(56% vs.56.1%).3).The course of cough in UIP group was 9(3.5,27.5)months,while 10(1,48)months in non-UIP group.Both groups had patients with cough at day time(44% vs.37.8%),dry cough(44% vs.35.4%),cough with expectoration(64% vs.68.3%)and identifiable precipitating factors(72% vs.76.8%),there was no statistical difference between the two groups(P> 0.05);In terms of cough nature,Single cough was more occurred in UIP patients than non-UIP patients(P=0.019).Daily cough scores,night cough scores,and median VAS scores in the UIP group were 2(2,3),1(0,2),3(1,5),while in non-UIP groups they were 2(1,3),1(0,2),and 3(1,5),respectively.There was no statistical difference between the two groups.4).UIP group showed poorer exercise tolerance(p=0.019).The median number of floors was 1(1,2)and 2(1,2.25)for UIP group and non-UIP group.5).UIP patients had poorer prognosis than non-UIP patients.Logistic regression analysis indicated that frequent cough was one of the prognostic indicators of ILD(OR 5.729,95%CI 2.085-15.744,P=0.001).2.Comparison of the basic patient information,pulmonary function tests,serum indicators and prognosis between group A(patients with multiple coughs)and group B(patients with infrequent coughs or without cough)1).Comparison of basic patient information: Of 107 eligible patients,43 were enrolled in the group A.The ratio of male to female was 1.2:1.The ratio of smoker to nonsmoker was 1:2.3.64 patients were enrolled in the group B.The male-to-female ratio was 1:1.1.The smoker-to-nonsmoker ratio was 1:2.0.The mean age was no difference between the two groups(55.26 years vs.55.28 years,P>0.05).The median number of floors was 1(1,2)and 2(1,3)for group A and group B,respectively(P=0.012).2).Pulmonary function tests: Pulmonary function test was performed in 77 patients,including 26 patients of group A and 51 patients of group B.FVC% predicted and TLC% predicted were significantly lower in group A than group B(65.54±17.96 vs.75.60±23.67,P=0.043;51.96±17.69 vs.70.93±16.87,P=0.014).30 patients(group A: 7 patients;group B: 23 patients)were examined for pulmonary function 3 to 6 months post-discharge.After treatment,FEV1,FVC,TLC,and DLco in both groups had a tendency to increase before the review,but there was no statistical significance.The group B had higher TLC% predicted after treatments while group A not(before treatments vs.after treatments: 76.91±17.99 vs.67.07±15.68,P<0.05).3).Serum indicators: KL-6 was significantly elevated in group A(1948 [834,3271] and group B(1159 [656,1915]).CA199 and KL-6 were significantly higher in group A than group B(P=0.001 and 0.014,respectively).However,no significant changes were observed for CA19-9 and KL-6 after treatments.4).Prognosis: Disease worsening was shown in 20(55.56%)patients of group A and 11(22.1%)patients of group B(P<0.01).The differences had statistical meaning.3.Comparison of the pulmonary function tests,serum indicators and prognosis between high-VAS-score group(? 5 points)and low-VAS-score group(< 5 points)1).Eligible patients were divided by VAS score to high-VAS-score group(n=30)and low-VAS-score group,n=77).Pulmonary function test was performed in 77 eligible patients,including 18 of high-VAS-score group and 59 of low-VAS-score group.Pulmonary function tests were not significantly different between high-VAS-score group and low-VAS-score group.The KL-6 levels in both groups increased significantly,but there was no statistical difference.CA19-9 level was higher in high-VAS-score group than low-VAS-score group(P=0.038).Four patients in high-VAS-score group and 26 patients in low-VAS-score group were followed up.TLC was improved in low-VAS-score group after treatments(P<0.05),but KL-6 and CA19-9 remained unchanged after treatments.2).Disease worsening was observed in 9(33.3%)and 22(30.6%)patients of highand low-VAS-score group.However,no significant differences were observed between high-VAS-score group and low-VAS-score group(P=0.79).Conclusions1.UIP patients are more likely to be old male smokers.Shortness of breath and cough are mostly presented in UIP patients and non-UIP patients.Exercise tolerance is impaired in UIP patients.Frequent cough was found to be one of the prognostic indicators of ILD.2.In our study,patients with frequent cough have poorer exercise tolerance and significantly higher CA19-9 level and KL-6 level and lower FVC and TLC,indicating the progression of interstitial lung diseases.Frequent cough maybe considered as a clinical marker of acute exacerbation of the disease.3.Patients with frequent cough have a higher chance of disease worsening and a trivial pulmonary function improvement,indicating poor response to treatments.For ILD patients with frequent cough,it is necessary to shorten the period of observation and evaluation.There is no obvious correlation between the severity of cough and pulmonary function in this study,and patients with severe coughs do not show improvements in pulmonary function after treatments,indicating the ineffectiveness of treatments in these patients.