Zhi-peng Tang, Jia-wei Wu, Yan-cheng Dai*, Ya-li Zhang, and Rong-rong Bi

1Department of Gastroenterology, Institute of Digestive Diseases,

2Department of Lung Function Laboratory, Longhua Hospital,

Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China

ORIGINAL ARTICLE

Relationship between Ulcerative Colitis and Lung Injuries△

Zhi-peng Tang1, Jia-wei Wu1, Yan-cheng Dai1*, Ya-li Zhang1, and Rong-rong Bi2

1Department of Gastroenterology, Institute of Digestive Diseases,

2Department of Lung Function Laboratory, Longhua Hospital,

Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China

ulcerative colitis; lung injury; Traditional Chinese Medicine

Objective To explore the relationship between ulcerative colitis (UC) and lung injuries by assessing their clinical manifestations and characteristics.

Methods From July 2009 to April 2012, 91 UC patients presenting to Longhua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study. According to the scores of disease activity index, the patients were divided into the mild, moderate, and severe groups. Meanwhile, the records of pulmonary symptoms, chest X-ray image, and pulmonary function were reviewed.

Results Sixty-eight (74.7%) patients had at least 1 pulmonary symptom, such as cough (38.5%), shortness of breath (27.5%), and expectoration (17.6%). And 77 (84.6%) had at least 1 ventilation abnormality. Vital capacity value was significantly lower in the severe group than that in the mild group (91.82%±10.38% vs. 98.92%±12.12%, p＜0.05).

Conclusions Lung injury is a common extraintestinal complication of UC. According to the theory in Traditional Chinese Medicine that the lung and large intestine are related, both the lungs and large intestine should be treated simultaneously.

Chin Med Sci J 2015; 30(2)：65-69

ULCERATIVE colitis (UC) is a diffuse inflammatory disease involving the mucosae of the rectum and colon; however, its pathogenesis is not fully understood. In China, the incidence rate for UC is about 11.62 per 100 000 people with a significantly increasing trend.1,2In addition to the typical symptoms, such as abdominal pain, diarrhea, and mucus and bloody purulent stool, pulmonary symptoms such as shortness of breath, a feeling of tightness in the chest, and cough are especially common in UC patients, and changes in chest radiographic results and pulmonary dysfunction might also occur clinically.3,4In this study, we analyzed the clinical manifestations and characteristics of UC patients complicated with lung injuries admitted to Longhua Hospital, Shanghai University of Traditional Chinese Medicine, with the aim of providing evidence for guidance in future clinical treatment.

PATIENTS AND METHODS

Patients

We made a retrospective study on 91 patients presenting with UC at Longhua Hospital between July 2009 and April 2012. The UC was diagnosed according to Understanding the Consensus on Diagnosis and Management of Inflammatory Bowel Disease.5,6

Those who were included in the study were patients who (1) matched the diagnostic criteria of UC; (2) were between 18 and 70 years of age; (3) had either mild and moderate UC (they were the majority of the patients) or severe UC but did not require emergency treatment or rescue; and (4) voluntarily participated in the study and signed the informed consent form. Patients excluded from the study were those who (1) were pregnant, lactating women or planning to get pregnant; (2) had severe complications, such as intestinal obstruction, intestinal perforation, cancer, polyps, colon cancer, colorectal cancer, and anal diseases; and (3) had mental disorders or severe primary diseases involving the cardiovascular, renal, or hepatic systems. Those withdrawn from the study were either patients who had been enrolled but did not match the inclusion criteria or who matched the inclusion criteria but with whom no follow-up could be done due to loss of contact information.

Observation items

General information on sex, age, smoking history, disease course, and medication history was recorded.

The range of the endoscopic lesions was classified as ulcerative proctitis, left-sided UC, and extensive UC based on the Montreal Classification of Inflammatory Bowel Disease.7

The Sutherland Index8was used to evaluate the disease activity. A score ≤2 indicated remission, 3-5 indicated mildly active, 6-10 indicated moderately active, and 11-12 indicated severely active. Based on disease severity, UC patients were divided into the mild, moderate, and severe groups.

Pulmonary symptoms, such as cough, expectoration, shortness of breath, and a feeling of tightness in the chest were recorded. Posteroanterior chest X-ray imaging was performed following the standard process.

A routine pulmonary function test was performed with the aid of a spirometer (MasterScreen Body/Diff, Jaeger Co., Hoechberg, Germany) and using the Knudsen equation. The detection error range of the spirometer was＜3% with an accuracy of 0.05 L. The pulmonary function mainly comprised the following parameter: vital capacity (VC), forced expiratory volume in one second (FEV1), percentage of FEV1 per forced vital capacity (FEV1/FVC), flow rate at 50% of FVC (FEF50), flow rate at 75% of FVC (FEF75), residual volume (RV), total lung capacity (TLC), ratio of RV to total lung capacity (RV/TLC), functional residual capacity, diffuson lung capacity for carbon monoxide (DLCO), and DLCO/alveolar ventilation. All tests were performed at the Pulmonary Function Room of Longhua Hospital.

Statistical analyses

SPSS 18.0 was used for the analyses. A normality test was performed for all measurement data. If data were distributed normally or quasi-normally, t-test for two independent samples was used for a comparison between the means of the two samples, and χ2analysis was used for comparisons among multiple samples. If the data were distributed abnormally, the non-parametric tests were used. P＜0.05 indicated statistical significance.

RESULTS

General information

Finally, 51 (56%) men and 40 (44%) women were reviewed in the study with a mean age of 40.88±12.65 years. Forty-five (49.5%) patients aged over 40 years. Of them, 15 (16.5%) first developed UC, and 76 (83.5%) were with relapsed chronic UC. Clinical characteristics of the 91 UC patients are shown in Table 1.

Table 1. Clinical characteristics of the studied UC patients

Pulmonary manifestations

Sixty-eight (74.7%) patients had at least 1 pulmonary system symptom, such as cough (38.5%), shortness of breath (27.5%), and expectoration (17.6%).

Chest X-ray images showed no obvious abnormalities in 12 (13.2%) patients. Of the others, 67 (73.6%) patients had deepened or thickened lung markings, 3 (3.3%) had deepened and disordered lung markings, 1 (1.1%) had disordered lung markings and increased shadows of the left hilum, 1 (1.1%) had disordered lung markings and patchy shadows in the left lower lung, 3 (3.3%) had nodular shadows, 2 (2.2%) had calcifications, 1 (1.1%) had linear opacities, and 1 (1.1%) had a few exudations.

Of the 91 UC patients, 77 (84.6%) had at least 1 abnormality in pulmonary ventilation functions; only 14 (16.4%) patients had normal pulmonary function. Among all the patients, the most prevalent abnormalities in pulmonary function were a decrease in FEV, such as DLCO (45/91, 49.5%), ratio of DLCO to alveolar volume (77/91, 84.6%), FEF75 (44/91, 48.4%), FEF50 (34/91, 37.4%), and VC (9/91, 9.9%), and an increase in RV (16/91, 17.5%).

Statistical analyses showed that no significant differences were found in the pulmonary function between smoking and non-smoking patients; among ulcerative proctitis, left-sided UC, and extensive UC patients; between patients in the active and remission phases (all P＞0.05, Table 2).

Statistical analyses revealed that only the VC value of the severe group was significantly lower than that of the mild group (P＜0.05). No statistical differences were found in the other pulmonary function parameters among the three groups (all P＞0.05, Table 3).

Treatment

Sixty-four (70%) patients were treated only with a Chinese herb. Twenty-seven (30%) were treated using integrative medicine, 12 (13%) with Chinese herb plus sulfasalazine and 15 (17%) with Chinese herb plus 5-aminosalicylate.

Table 2. Comparisons of pulmonary function between smoking and non-smoking patients; among ulcerative proctitis, left-sided UC, and extensive UC patients; between patients in the active and remission phases§

Table 3. Comparisons of the pulmonary function among UC patients with different disease severities§

DISCUSSION

The incidence rate of complications from lung injuries are rather high in UC patients. Mikha?lova9reported that 30 out of 58 (51.7%) patients with inflammatory bowel diseases had abnormal pulmonary functions. Herrlinger et al10found that respiratory symptoms were absent in about one-half of UC patients with lung injuries, and abnormal pulmonary functions persisted even though the patients were in remission. Zhang et al11revealed that 58.6% of UC patients had respiratory symptoms of shortness of breath, cough, and a feeling of tightness in the chest, of which shortness of breath was the main manifestation in patients with different stages and varying severities of UC. Moreover, of 63.3% patients with abnormal pulmonary functions, the abnormalities were clearly obvious in those with mild or moderate severities in which the damage to the lungs was mainly manifested as airflow limitations and decreased diffusing capacity.

UC lung injuries are based on several physiological mechanisms. Morphologically, most of the organs in the respiratory and digestive systems have developed from the primitive gut; therefore, the lungs, trachea, and intestines have the same structure and origin. From the point of view of the mucosal immune system, mucosae that cover the gastrointestinal and respiratory tracts are part of the common mucosal immune system, which regulates the human immune response. From the point of view of the nerve–endocrine–immune network theory, in addition to being a digestive organ, the intestine is also a massive and complex endocrine organ (i.e., the “second brain”) that regulates gastrointestinal movements, respiratory ventilation functions, and endocrine functions through mediations of a series of neurotransmitters.12

Our study focused on the extraintestinal manifestations of UC. Our data showed that, in most of the UC patients studied, chest symptoms, abnormal chest X-rays results, and varying degrees of pulmonary dysfunction had occurred, indicating that the majority of patients suffered from pulmonary damages manifested mainly as smallairway dysfunction and impairment of diffusion capacity, which were often positively correlated with UC severity (the more severe the disease is, the less the VC value is). These findings suggest that UC lesions are correlated with lung injuries, which definitely deserves more attention in future clinical practice.

Traditional Chinese Medicine believes that the lung and the large intestine are interior-exteriorly related through the human meridian system and that these two organs are inseparably dependent on each other because they influence and complement each other in multiple aspects involving the physiological and pathological processes. Yan et al13established the UC rat model using the allergenic model that uses rabbit intestine mucosa tissue and a model that uses trinitrobenzene sulfonic acid dissolved in ethanol to explore the material basis of the above theory and found pathological manifestations of intestinal and pulmonary injuries in the modeled rats. They also found that abnormal protein expressions of Bcl-2 and Bax induced apoptosis in the pulmonary tissues, and that tumor necrosis factor α, interleukin 1β, superoxide dismutase, and malondialdehyde might be the common materials in intestinal and pulmonary damage in UC patients.14,15The theory has effectively guided current clinical practice, and unexpected clinical efficacy usually results in treatments of both the lung and intestine.

In addition to the typical intestinal symptoms, such as abdominal pain, diarrhea, and mucus and bloody purulent stool, pulmonary symptoms, such as short of breath, a feeling of tightness in the chest, and cough are also observed in UC patients, which severely affects their quality of life.16Current therapeutic strategies andobjectives for the treatment of UC have involved steps to improve the patient’s quality of life, induce and maintain clinical remission and mucosal healing, and prevent complications.17Unfortunately, there are no specific treatments for UC-associated lung injuries. Black et al18reported that inhalation of corticosteroids was efficacious for UC-associated chronic bronchitis. Goeminne et al19found that immunomodulatory therapy had certain efficacy in the treatment of UC-associated bronchiectasis, they suggested that the associated safety issues be thoroughly evaluated. Numerous trials and studies have proved the exact efficacy of Chinese herbal treatment guided by syndrome differentiation and Traditional Chinese Medicine treatment in UC patients.20-22

In conclusion, lung injury is a common extraintestinal complication of UC. According to the theory of the lung and the large intestine being interior-exteriorly related as proposed by Traditional Chinese Medicine, simultaneous treatment should be performed on both the lung and intestine, and treating the large intestine is more important than treating the lungs. This might provide a new therapeutic approach for UC complicated by lung injuries and is worth further investigation.

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for publication November 24, 2014.

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△Supported by the New Project of Traditional Chinese Medicine of Shanghai Health and Family Planning Commission for the next three years (LH02.28.006).