Co-morbid illnesses in patients with respiratory disease

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respiratory disease

Kouji KANEMOTO¹, Hiroaki SATOH², Hiroichi ISHIKAWA¹, Masaaki SUMI³, Morio OHTSUKA²

1 Division of Respiratory Medicine, Tsukuba Medical Center Hospital, Tsukuba, Japonya,

2 Division of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japonya, 3 Division of Respiratory Medicine, Kensei General Hospital, Japonya.

ÖZET

Solunum hastalığı olanlarda eşlik eden hastalıklar

İlerleyen yaşla birlikte daha fazla sayıda hastaya bir veya daha fazla ciddi hastalık tanısı konulacaktır. Bu çalışma solu- num sistemi hastalığı olan hastalarda eşlik eden hastalık sıklığının değerlendirilmesi, yaşlı ve daha genç hastalardaki eşlik eden hastalık sıklığını karşılaştırmak üzere yapıldı. Japonya’da Ocak 1990-Mart 2005 tarihleri arasında üç hastaneye baş- vuran 2764 hastanın dosya incelemesi yapıldı. Solunum hastalığı olan 2764 hastanın %69.5’inde eşlik eden hastalık sap- tandı. Yetmiş yaş ve üstünde olan 1150 hastanın %83.9’unda ek hastalık vardı. Solunum sistemi hastalığı olan hastalarda eşlik eden hastalık prevalansının açıkça arttığı (p= 0.0001), en fazla artışın 50 yaş sonrasında ortaya çıktığı bulundu. So- lunum sistemi hastalığı olanlarda artan yaşla birlikte Charlson indeksi yüksekti (p= 0.0001). Hem yaşlı (≥ 70 yaş) hem de genç (< 70 yaş) gruptaki hastalarda, eşlik eden hastalıkların tanısal prosedür seçimini etkilemediği belirlendi. Malignite dı- şı solunum hastalığı olanlarda ek hastalık varlığı tedavi kararını etkilememekle beraber malignitesi olan yaşlı hastalarda ek hastalık olmasının standart tedavi kararını olumsuz olarak etkilediği saptandı. Klinik araştırma sadece eşlik eden has- talığı olmayan yaşlı hastalarda uygun tedavileri değil ayrıca ek hastalığı olanları da kapsamalıdır. Ek hastalıkların farkın- da olunması özel ve dikkatli bakım gerektiren solunum hastalığı olan geniş bir yaşlı hasta grubunda uygun desteğin plan- lanmasına ve yeterli tedavi uygulanmasını sağlayacaktır.

Anahtar Kelimeler: Eşlik eden hastalık, solunum hastalığı, tanı, tedavi, akciğer kanseri, kronik obstrüktif akciğer has- talığı.

Yazışma Adresi (Address for Correspondence):

Hiroaki SATOH, MD, Division of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-City, Ibaraki, 305-8575, JAPAN

e-mail: hirosato@md.tsukuba.ac.jp

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For many middle-aged and elderly patients, serious co-morbid illnesses, which occur with increasing frequency as age increases, may have some clinical implications. This same observa- tion applied to the co-morbid illnesses in patients with respiratory disease, and many previ- ous authors mainly studied co-morbid illnesses in patients with chronic obstructive pulmonary disease (COPD) and lung cancer (1-13). Chro- nic respiratory diseases including COPD and idiopathic interstitial pneumonia have their on- set in individuals during their age of 60s and 70s (14,15). For these diseases, smoking is the major risk factor, and it is also a risk factor for atherosclerosis, cancer and coronary artery disease (16-18). Thus, the potential for severe and significant co-morbid illnesses influencing the course and natural history of respiratory di-

sease is substantial. In addition, the co-morbid illnesses may adversely influence the selection of therapy and they necessitate modifications of the chosen therapy, which is often less aggressive for the elderly due to greater toxicity. The- refore, their presence may also be an indicator of the complexity of the clinical need of each patient.

In this study, we analyzed the age-specific prevalence of co-morbid illnesses for patients with various malignant and non-malignant respiratory diseases. The objects of this study were:

1. To evaluate the frequency of co-morbid illnesses in patients with both malignant and non-malignant respiratory diseases,

2. To compare the frequency of co-morbidity between these two groups of patients,

SUMMARY

Co-morbid illnesses in patients with respiratory disease

Kouji KANEMOTO¹, Hiroaki SATOH², Hiroichi ISHIKAWA¹, Masaaki SUMI³, Morio OHTSUKA²

1Division of Respiratory Medicine, Tsukuba Medical Center Hospital, Tsukuba, Japan,

2Division of Respiratory Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan,

3Division of Respiratory Medicine, Kensei General Hospital, Japan.

With the rising age, more patients will be diagnosed with one or more other serious illnesses. This study was undertaken to evaluate the frequency of co-morbid illnesses in patients with respiratory diseases, and to compare the frequency betwe- en the elderly and the younger patients. We performed chart review of 2764 patients with respiratory disease who admit- ted in three hospitals in Japan between January 1990 and March 2005. Co-morbid illnesses were observed in 69.5% of 2764 patients with respiratory disease. In 1150 patients 70 years or older, 83.9% of them had co-morbid illnesses. The prevalen- ce of co-morbid illnesses in patients with respiratory disease clearly rose with increasing age (p= 0.0001), the largest incre- ase occurring after the age of 50. Charlson index in patients with respiratory disease clearly rose with increasing age (p=

0.0001). In both elderly (≥ 70 years) or younger (< 70 years) groups of patients, co-morbid illnesses did not influence on the choice of diagnostic procedure. Although the presence of co-morbid illnesses in our patients with non-malignant respira- tory disease did not influence on the choice of treatment, however, the presence of co-morbid illnesses in elderly patients with malignant respiratory disease apparently discouraged the choice of standard therapy. Clinical research should add- ress appropriate therapies not only for the elderly patients without co-morbid illness but also for those with co-morbid ill- nesses. Being aware of the co-morbid illnesses will allow improved management and the planning of appropriate support to a wide range of elderly patients with respiratory disease with important and peculiar needs for care.

Key Words: Co-morbid illness, respiratory disease, diagnosis, therapy, lung cancer, chronic obstructive pulmonary disease.

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3. To compare the frequency between the younger patients and the elderly ones.

MATERIALS and METHODS Patient Population

All patients who admitted in Respiratory Divisi- ons of Tsukuba University Hospital, Tsukuba Medical Center Hospital and Kensei General Hospital for symptoms of respiratory disease and found to have it between January 1990 and March 2005 were included. Patient records were retrospectively reviewed to obtain data on patient characteristics, co-morbid illnesses, treatment, and clinical outcomes. In the event of multiple admissions for the same patient within the sampling period, one admission was chosen to be included at random.

Co-morbid illnesses were defined as follows:

cardiac co-morbid illness: presence of coronary artery disease or congestive heart failure; renal:

pre- and co-existing renal disease with a docu- mented abnormal serum creatinine level; hepatic: pre- and co-existing viral or toxic hepato- pathy; disorders of the central nervous system:

presence of symptomatic acute or chronic vascular or nonvascular encephalopathy, with or without dementia; diabetes mellitus: diagnosis of intolerance to glucose and treat with oral antidi- abetics or insulin; synchronous neoplastic illness: any solid tumor active at the time of pre- sentation or requiring antineoplastic treatment within the preceding year, and other tumors were defined as metachronous.

Co-Morbidity

Co-morbidity was quantified according to the Charlson Index (19,20). This index has been developed to predict the mortality of patients with chronic diseases. It assigns to each disease a score that is proportional to disease-related risk of death. A score 1 is allocated to myo- cardial infarction, congestive heart failure, pe- ripheral vascular disease, cerebrovascular disease, dementia, chronic respiratory disease, connective tissue disease, ulcer disease, mild liver disease, and diabetes. A score 2 is allocated to diabetes with end-organ damage, hemip- legia, renal disease, and malignancies, inclu-

ding leukemia and lymphoma. A score 3 is attributed to moderate or severe liver disease, while acquired immunodeficiency syndrome and metastatic malignancies are attributed a score of 6.

Statistical Analysis

Chi-square test was applied to elucidate the difference between two independent groups or more. Kruskal-Wallis test was used to evaluate the difference among three or more independent groups. Only results with p less than 0.01 were regarded as significant.

RESULTS

There were 866 patients with malignant and 1898 patients with non-malignant respiratory disease. Table 1 depicts the clinicopathological features of these patients. Overall, co-morbid illness were observed in 1921 (69.5%) of 2764 patients with respiratory disease. In 1150 patients 70 years or older, co-morbid illnesses were observed in 965 (83.9%) patients. The prevalence of co-morbid illness was higher among patients with malignant respiratory disease compared with those with non-malignant (p=

0.0001): 645 (74.5%) of 866 patients with malignant respiratory disease and 1276 (67.2%) of 1898 patients with non-malignant respiratory disease.

Table 2 shows prevalence of non-malignant co- morbid illness. The prevalence was highest for cardiovascular (35.9%), metabolic and endocrinological (18.7%), and gastrointestinal system (18.2%). The most common co-morbid illnesses were hypertension (26.6%), diabetes mellitus (11.8%). Coronary disease (6.5%) and cerebrovascular disease (5.1%) were also observed (Table 2).

Table 3 depicts the age-specific prevalence of co-morbid illnesses among patients with respiratory disease. The prevalence of co-morbid illnesses in patients with respiratory disease clearly rose with increasing age (p= 0.0001), the largest increase occurring after the age of 50.

Co-morbid illnesses more than 2 also increased with age. Table 3 also shows the age-specific Charlson index among patients with respiratory

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Table 2. Prevalence of non-malignant co-morbid illness among patients with respiratory disease.

Co-morbid illness Number of patient

Cardiovascular 992 (35.9%)

Hypertension 735

Arrhythmia 175

Coronary disease 179

Metabolic and endocrinological 518 (18.7%)

Diabetes mellitus 325

Hyperlipidemia 146

Gastrointestinal 502 (18.2%)

Peptic ulcer 205

Liver dysfunction 99

Neurological 436 (15.8%)

Cerebrovascular disease 141

Sleep disturbance 209

Respiratory 430 (15.6%)

COPD 157

Tuberculosis (active, sequelae) 99

Bronchial asthma 73

Head and neck and 280 (10.1%) ophthalmological

Urological 263 (9.5%)

Prostate hyperplasia 127 Nephropathy, renal failure 51

Orthopedical 212 (7.7%)

Others 147 (5.3%)

COPD: Chronic obstructive pulmonary disease.

Table 3. Age-specific prevalence of co-morbid illness and Charlson index among patients with respiratory dis- ease.

Number of co-morbid illness Charlson index

Age (years) n None (%) One (%) ≥ 2 (%) None (%) One (%) ≥ 2 (%)

40 < 369 268 (72.6) 70 (19.0) 31 (8.4) 308 (83.5) 43 (11.7) 18 (4.9)

≤ 40-< 50 182 92 (50.5) 51 (28.0) 39 (21.4) 130 (71.4) 32 (17.6) 20 (11.0)

≤ 50-< 60 407 158 (38.8) 138 (33.9) 111 (27.3) 265 (65.1) 105 (25.8) 37 (9.1)

≤ 60-< 70 656 140 (21.3) 193 (29.4) 323 (49.2) 299 (45.6) 209 (31.9) 148 (22.6)

≤ 70-< 80 860 139 (16.2) 220 (25.6) 501 (58.3) 298 (34.7) 279 (32.4) 283 (32.9)

≤ 80 290 46 (15.9) 64 (22.1) 180 (62.1) 101 (34.8) 107 (36.9) 82 (28.3) Table 1. Characteristics of 2764 patients with

respiratory diseases.

Malignant Non-malignant

Number of patients 866 1898

Age (median, 69 (19-94) 65 (16-98) range), Yr

Male/female 642/224 1185/713

Diagnosis

Primary lung cancer 782 Metastatic lung tumor 35 Mediastinal tumor 24 Malignant lymphoma 11

Mesothelioma 5

Others 9

Pneumonia, 537 bronchitis, pleuritis

Bronchial asthma 327

COPD 244

IIP, CDPF 184

Pneumothorax 88

Sarcoidosis 76

Sleep apnea syndrome 66

Bronchiectasis 57

Tuberculosis 37

Pulmonary thromboembolism 34

Pneumoconiosis 23

Pulmonary mycoses 22

Others 203

IIP: Idiopathic interstitial pneumonia, CDPF: Collagen disease related pulmonary fibrosis, COPD: Chronic obstructive pulmonary disease.

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disease. The index clearly rose with increasing age (p= 0.0001), the largest increase occurring after the age of 60. The index more than 2 also increased with age.

The age-specific prevalence of synchronous and metachronous malignant disease among patients with malignant and non-malignant respiratory disease are shown in Table 4. Three of the most common synchronous malignant co-mor-

bid illnesses were prostate cancer, gastric cancer, and hepatic cancer. Gastric cancer, colon cancer, and lung cancer were three of the most common metachronous malignant co-morbid illnesses. Therefore, aero-digestive tract tumors were common in our patients.

Table 5 shows the prevalence of co-morbid illness and invasive diagnostic procedures in pati-

Table 4. Prevalence of synchronous and metachronous malignant co-morbid illness among patients with respi- ratory disease.

Number of patients Number of patients

Co-morbid illness Synchronous Metachronous Co-morbid illness Synchronous Metachronous

Respiratory Urogenital cancer

Lung cancer 4 21 Prostate cancer 17 5

Neurological Renal cancer 5 4

Brain tumor 3 1 Bladder cancer 5 13

Gastrointestinal Uterus cancer 2 10

Gastric cancer 13 53 Others 0 3

Colon cancer 7 30 Head and neck cancer 7 18

Esophageal cancer 0 9 Orthopedic tumor 2 2

Duodenal cancer 0 3 Hematological malignancy 8 3

Hepatic cancer 9 3 Dermal tumor 3 5

Others 5 11

Endocrinological tumor

Breast cancer 3 18

Thyroid cancer 3 9

Others 0 3

Table 5. Patients with respiratory disease who received or did not receive invasive diagnostic procedures due to co-morbid illnesses.

Age (years)

Respiratory disease 70 ≥ 70 < p

No. of patients with malignant respiratory disease

With invasive diagnostic procedure 410 442

Without invasive diagnostic procedure 0.1068

due to co-morbid illnesses 10 4

No. of patients with non-malignant respiratory disease

With invasive diagnostic procedure 727 1167

Without invasive diagnostic procedure 0.1617

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ents with malignant and non-malignant respiratory disease. The procedures included bronc- hoscopy, transthoracic biopsy, and video-assis- ted thoracic surgery. In both elderly (≥ 70 years) or younger (< 70 years) groups of patients, co- morbid illnesses did not influence on the choice of diagnostic procedure. There was no statistical difference in the influence of co-morbid illnesses between the two age groups.

In Table 6, we showed the prevalence of co-morbid illness and standard therapy in patients with malignant and non-malignant respiratory disease. Among the 866 patients with malignant respiratory disease, 57 patients was not received standard therapy due to their co-morbid illnesses such as COPD, renal failure, coronary disease, liver dysfunction, and cerebrovascular disease. In elderly patients with malignant respiratory disease, the prevalence of co-morbid disease did influence on the choice of standard therapy (p= 0.0001). On the other hand, the prevalence of co-morbid disease in elderly patients with non-malignant respiratory disease did not influence on the choice of therapy.

DISCUSSION

This hospital-based study presented a review of the magnitude of the problem of clinically rele- vant co-morbid illnesses in 2764 patients with respiratory disease. Overall, co-morbid illnesses were observed in 69.5% of them. In 1150 patients 70 years or older, 83.9% had co-morbid ill-

nesses. The prevalence of co-morbid illnesses clearly rose with increasing age, the largest increase occurring after the age of 50. Co-morbid illnesses more than 2 also increased with age. In addition, the Charlson index clearly rose with increasing age, the largest increase occurring after the age of 60. The index more than 2 also increased with age. The prevalence was highest for cardiovascular, metabolic and gastrointestinal system. Among the co-morbid illnesses, hypertension and diabetes mellitus were the most common co-morbid illnesses. Several authors indicated that the prevalence of co-morbid illnesses clearly increased with age for patients with cancers at various sites (12,21-23). Among the reports, Janssen-Heijnen showed that in non-small cell lung cancer patients aged 70 or older, the prevalence of co-morbid Illness was 73% for men and 61% of women (12). In their re- port, the most frequent co-morbid illnesses in elderly men were cardiovascular (31%) and COPD (29%); in elderly women the most common illnesses were cardiovascular diseases (22%), hypertension (22%), and COPD (20%) (12).

A comparison with their data showed that our prevalence rate for hypertension was high and that for COPD was lower. Comparison with prevalence reported by others can be hampered by differences in the processes of ascertainment, record keeping, and registration. The results are also depended on the aim of the assessment of co-morbid illness.

Table 6. Patients with respiratory disease who received or did not receive standard therapy due to co-morbid illnesses.

Age (years)

Respiratory disease 70 ≥ 70 < p

No. of patients with malignant respiratory disease

With standard therapy 375 434

Without standard therapy 0.0001

No. of patients with non-malignant respiratory disease

With standard therapy 726 1166

Without standard therapy 0.2123

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In general, the co-morbid illnesses may adversely influence the selection of therapy and they necessitate modifications of the chosen therapy, which is often less aggressive for them due to greater toxicity. An influence of co-morbid illness and age on therapeutic decision-making in lung and colorectal cancer has been reported (2,24). Although the presence of co-morbid illnesses in our patients with non-malignant respiratory disease did not influence on the choice of treatment, however, the presence of co-morbid illnesses in those with malignant respiratory disease, especially in the elderly ones, apparently discouraged the choice of standard therapy.

As with any retrospective study, the individuals initially recording the patients’ history were not aware of this research on co-morbid illnesses.

Therefore, some pertinent information on co- morbid illnesses may not have been recorded or may have been recorded incorrectly. In addition, patients who received dose-reduced anticancer chemotherapy, dose-reduced radiotherapy, and limited surgery due to co-morbid illnesses were evaluated as those who had standard therapy.

Only patients who did receive less invasive therapy or supportive care other than standard therapy were evaluated as those who did not have appropriate therapy. Therefore, more patients than we showed might be influenced on the choice of standard therapy.

In our study population, 83.9% of the elderly patients with respiratory disease suffered from co- morbid illnesses. Although the presence of co- morbid illnesses in our patients with non-malignant respiratory disease did not influence on the choice of treatment, however, the presence of co-morbid illnesses in elderly patients with malignant respiratory disease apparently discouraged the choice of standard therapy. Clinical research would address appropriate therapies not only for the patients without co-morbid illnesses but also for those with co-morbid illness. More- over, being aware of the co-morbid illnesses will allow improved management and the planning of appropriate support to a wide range of elderly patients with respiratory disease with important and peculiar needs for care.

ACKNOWLEDGEMENT

This study was supported by Chiyoda Health Science Foundation.

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