Abstract
BACKGROUND:
Cachexia has been associated with chronic lung disease (pulmonary cachexia syndrome), which is associated with increased mortality. However, studies that looked into this association was relatively small, and national level data are lacking. Herein, we aim to study the association between chronic obstructive lung disease (COPD) and cachexia.
RESEARCH QUESTION:
Do patients with COPD and cachexia has worse inpatient outcomes in comparison to those with no cachexia?
STUDY DESIGN AND METHODS:
We used the Nationwide Readmissions Database from 2016 to 2019, extracting adult patients with a primary diagnosis of COPD who were admitted between January and November of each year studied. We excluded patients with missing data on event time or length of stay. Furthermore, we excluded all cases with cormobidities associated with cachexia. We used SAS 9.4 for data exploration and analysis.
RESULTS:
We included 1,446,431 COPD-related weighted hospitalizations for which 115,276 cases (7.9%) had a concurrent diagnosis of cachexia (or cachexia-related diagnoses). Overall, patients with cachexia (COPD-C), compared to patients with COPD and no cachexia (COPD-NC), were older (mean age 69 vs. 66 years, respectively, P < 0.001) with similar gender distribution (58%). COPD-C patients had more inpatient complications including cardiac arrest, and use of mechanical ventilation (P < 0.001). Furthermore, they had longer mean lengths of stay (5.2 days vs. 3.8 days, P < 0.001). In-hospital mortality during index, admission was significantly higher in these patients at 2.2% compared to 0.5% for COPD-NC (P < 0.001).
CONCLUSION:
COPD-related cachexia is associated with increased inpatient mortality, resource utilization, and prolonged hospitalization.
Keywords: Cachexia, chronic obstructive pulmonary disease, inpatient mortality, Nationwide Readmissions Database
Cachexia is a syndrome of unintended weight loss that cannot be fully reversed with feeding.[1] It has been associated with multiple chronic diseases including chronic obstructive pulmonary disease (COPD).[2,3] Although the term “pulmonary cachexia” could be used to describe cachexia associated with chronic lung disease, it is most frequently seen and reported in patient with COPD.[4] The prevalence of cachexia in patient with COPD is around 25%–50%.[4,5,6] This wide variation could be related to different study population and definitions. Prior studies suggested that pulmonary cachexia syndrome (COPD-related cachexia) as a poor prognostic factor for mortality independent of disease stage.[7] However, most of the studies are either single center, from clinical trials or have focused on outpatient settings.[7,8,9,10] Data on cachexia as a prognosticator in hospitalized patients with acute COPD exacerbation are sparse. The goal of the study is to evaluate the association of cachexia with inpatient mortality and 30-day readmission in patients hospitalized with a primary diagnosis of COPD.
Methods
Data source
This study is a retrospective population-based study using data from the Healthcare Cost and Utilization Project (HCUP). The Agency for Healthcare Research and Quality (AHRQ) is a federal agency under the Department of Health and Human Services. One of its products is HCUP. HCUP is a comprehensive set of all payer health-care data that are based on billing records (inpatient stays, emergency department visits, and ambulatory care). Nationwide readmission database (NRD) is an HCUP product, i.e., derived from state level data and is meant to study factors affecting inpatient mortality and 30-day readmission for patients of all ages regardless of the payer. It is the largest publicly available database for inpatient populations in the United States containing over 17 million records every year, representing all discharges in a given year (which are close to 35 million yearly).[11]
The NRD database from the end of 2015 contains up to 40 variables that includes International Classification of Diseases, 10th Edition (ICD-10) codes for medical conditions addressed during hospitalization. It also contains up to 30 variables that include ICD-10 codes for procedures performed during hospital stay. The data were extracted using the ICD-10 codes to identify subjects.
For this study, we utilized the NRD database for the years 2016–2019. We followed the data use agreement and guidelines recommended by AHRQ. The database is publicly available and contains de-identified information. Hence, the study was deemed exempt by our institutional review board.
Study population
The inclusion criteria included all adult patients (older than 18 years) with a primary diagnosis (I10_Dx1) of COPD who were discharged from January to November in years 2016–2019, with a concurrent diagnosis of cachexia or other weight loss-related diagnoses [Supplementary Tables 1-12 (1MB, pdf) for codes used for case definition). To increase study specificity for COPD cachexia syndrome, we excluded all patients with a concurrent diagnosis of acquired immunodeficiency syndrome (AIDS), heart failure, malignancy (including hematological and solid cancers), advanced liver disease, end-stage renal disease, and certain neurological disorders [Supplementary Tables 1-12 (1MB, pdf) for codes used for definition). Thus, pulmonary cachexia is identified if the patient had a primary diagnosis of COPD in addition to a weight loss-related diagnosis after applying the exclusions above. The HCUP team had validated these ICD-10 codes for such diagnoses.[12] Since we cannot follow-up the patient across the years using the NRD database and because we are interested in assessing readmission outcomes, we did not include discharges in December of each year. We also excluded patients with missing values for length of stay (LOS) or event time (NRD days to event) which are necessary for evaluating readmissions. When calculating readmission rate, we did not include patients who died during index hospitalization in the denominator [Figure 1].
Supplementary Table 1.
Case definition based on Internation Classification for Diseases, Tenth Revision (ICD-10) codes for Chronic Obstructive Lung Disease (COPD)
| ICD-10-CM for COPD diagnosis | ICD-10-CM code description |
|---|---|
| J411 | Mucopurulent chronic bronchitis |
| J418 | Mixed simple and mucopurulent chronic bronchitis |
| J42 | Unspecified chronic bronchitis |
| J431 | Panlobular emphysema |
| J432 | Centrilobular emphysema |
| J438 | Other emphysema |
| J439 | Emphysema, unspecified |
| J440 | Chronic obstructive pulmonary disease with (acute) lower respiratory infection |
| J441 | Chronic obstructive pulmonary disease with (acute) exacerbation |
| J449 | Chronic obstructive pulmonary disease, unspecified |
COPD=Chronic obstructive lung disease, ICD-10-CM=International Classification of Diseases, 10th Edition Clinical Modification
Figure 1.
Flow diagram showing study enrollments. HIV: Human immunodeficiency virus. HF: Heart failure. ESRD: End-stage renal disease
Supplementary Table 2.
Case definition based on Internation Classification for Diseases, Tenth Revision (ICD-10) codes for cachexia and cachexia-related diagnoses
| Code for malnutrition | Description |
|---|---|
| E40 | Kwashiorkor |
| E41 | Nutritional marasmus |
| E42 | Marasmic kwashiorkor |
| E43 | Unspecified severe protein-calorie malnutrition |
| E440 | Moderate protein-calorie malnutrition |
| E441 | Mild protein-calorie malnutrition |
| E46 | Unspecified protein-calorie malnutrition |
| E640 | Sequelae of protein-calorie malnutrition |
| M6284 | Sarcopenia |
| R627 | Adult failure to thrive |
| R634 | Abnormal weight loss |
| R636 | Underweight |
| R64 | Cachexia |
| Z681 | BMI 19 or less, adult |
BMI=Body mass index, ICD-10-CM=International Classification of Diseases, 10th Edition Clinical Modification
Supplementary Table 3.
Case definition based on Internation Classification for Diseases, Tenth Revision (ICD-10) codes for heart failure
| ICD-10-CM diagnosis to define heart failure | ICD-10-CM code description |
|---|---|
| I0981 | Rheumatic heart failure |
| I110 | Hypertensive heart disease with heart failure |
| I130 | Hypertensive heart and chronic kidney disease with heart failure and stage 1 through stage 4 chronic kidney disease or unspecified chronic kidney disease |
| I132 | Hypertensive heart and chronic kidney disease with heart failure and with stage 5 chronic kidney disease or end-stage renal disease |
| I501 | Left ventricular failure, unspecified |
| I5020 | Unspecified systolic (congestive) heart failure |
| I5021 | Acute systolic (congestive) heart failure |
| I5022 | Chronic systolic (congestive) heart failure |
| I5023 | Acute on chronic systolic (congestive) heart failure |
| I5030 | Unspecified diastolic (congestive) heart failure |
| I5031 | Acute diastolic (congestive) heart failure |
| I5032 | Chronic diastolic (congestive) heart failure |
| I5033 | Acute on chronic diastolic (congestive) heart failure |
| I5040 | Unspecified combined systolic (congestive) and diastolic (congestive) heart failure |
| I5041 | Acute combined systolic (congestive) and diastolic (congestive) heart failure |
| I5042 | Chronic combined systolic (congestive) and diastolic (congestive) heart failure |
| I5043 | Acute on chronic combined systolic (congestive) and diastolic (congestive) heart failure |
| I50810 | Right heart failure, unspecified |
| I50811 | Acute right heart failure |
| I50812 | Chronic right heart failure |
| I50813 | Acute on chronic right heart failure |
| I50814 | Right heart failure due to left heart failure |
| I5082 | Biventricular heart failure |
| I5083 | High-output heart failure |
| I5084 | End-stage heart failure |
| I5089 | Other heart failure |
| I509 | Heart failure, unspecified |
| I5181 | Takotsubo syndrome |
| I97130 | Postprocedural heart failure following cardiac surgery |
| I97131 | Postprocedural heart failure following other surgery |
| O29121 | Cardiac failure due to anesthesia during pregnancy, first trimester |
| O29122 | Cardiac failure due to anesthesia during pregnancy, second trimester |
| O29123 | Cardiac failure due to anesthesia during pregnancy, third trimester |
| O29129 | Cardiac failure due to anesthesia during pregnancy, unspecified trimester |
| R570 | Cardiogenic shock |
ICD-10-CM=International Classification of Diseases, 10th Edition Clinical Modification
Supplementary Table 4.
Case definition based on Internation Classification for Diseases, Tenth Revision (ICD-10) codes for encephalopathies
| ICD-10-CM diagnosis of specific neurological conditions excluded | ICD-10-CM code description |
|---|---|
| E7500 | GM2 gangliosidosis, unspecified |
| E7501 | Sandhoff disease |
| E7502 | Tay-Sachs disease |
| E7509 | Other GM2 gangliosidosis |
| E7510 | Unspecified gangliosidosis |
| E7511 | Mucolipidosis IV |
| E7519 | Other gangliosidosis |
| E7523 | Krabbe disease |
| E7525 | Metachromatic leukodystrophy |
| E7526 | Sulfatase deficiency |
| E7529 | Other sphingolipidoses |
| E754 | Neuronal ceroid lipofuscinosis |
| F05 | Delirium due to known physiological condition |
| F842 | Rett’s syndrome |
| G35 | Multiple sclerosis |
| G360 | Neuromyelitis optica (Devic) |
| G368 | Other specified acute disseminated demyelination |
| G369 | Acute disseminated demyelination, unspecified |
| G370 | Diffuse sclerosis of the central nervous system |
| G371 | Central demyelination of corpus callosum |
| G372 | Central pontine myelinolysis |
| G373 | Acute transverse myelitis in demyelinating disease of central nervous system |
| G374 | Subacute necrotizing myelitis of central nervous system |
| G375 | Concentric sclerosis (Balo) of central nervous system |
| G378 | Other specified demyelinating diseases of central nervous system |
| G379 | Demyelinating disease of central nervous system, unspecified |
| G47411 | Narcolepsy with cataplexy |
| G47419 | Narcolepsy without cataplexy |
| G47421 | Narcolepsy in conditions classified elsewhere with cataplexy |
| G47429 | Narcolepsy in conditions classified elsewhere without cataplexy |
| G890 | Central pain syndrome |
| G910 | Communicating hydrocephalus |
| G911 | Obstructive hydrocephalus |
| G912 | Idiopathic normal pressure hydrocephalus |
| G913 | Posttraumatic hydrocephalus, unspecified |
| G914 | Hydrocephalus in diseases classified elsewhere |
| G918 | Other hydrocephalus |
| G919 | Hydrocephalus, unspecified |
| G930 | Cerebral cysts |
| G9340 | Encephalopathy, unspecified |
| G9341 | Metabolic encephalopathy |
| G9349 | Other encephalopathies |
| G935 | Compression of brain |
| G936 | Cerebral edema |
| G937 | Reye’s syndrome |
| G9381 | Temporal sclerosis |
| G9382 | Brain death |
| G9389 | Other specified disorders of the brain |
| G939 | Disorder of brain, unspecified |
| G94 | Other disorders of the brain in diseases classified elsewhere |
| O99350 | Diseases of the nervous system complicating pregnancy, unspecified trimester |
| O99351 | Diseases of the nervous system complicating pregnancy, first trimester |
| O99352 | Diseases of the nervous system complicating pregnancy, second trimester |
| O99353 | Diseases of the nervous system complicating pregnancy, third trimester |
| O99354 | Diseases of the nervous system complicating childbirth |
| O99355 | Diseases of the nervous system complicating the puerperium |
| P9160 | HIE, unspecified |
| P9161 | Mild HIE |
| P9162 | Moderate HIE |
| P9163 | Severe HIE |
HIE=Hypoxic ischemic encephalopathy, ICD-10-CM=International Classification of Diseases, 10th Edition Clinical Modification
Supplementary Table 5.
Case definition based on Internation Classification for Diseases, Tenth Revision (ICD-10) codes for liver failure
| ICD-10-CM diagnosis for liver failure | ICD-10-CM code description |
|---|---|
| B190 | Unspecified viral hepatitis with hepatic coma |
| B1911 | Unspecified viral hepatitis B with hepatic coma |
| B1921 | Unspecified viral hepatitis C with hepatic coma |
| I8500 | Esophageal varices without bleeding |
| I8501 | Esophageal varices with bleeding |
| I8510 | Secondary esophageal varices without bleeding |
| I8511 | Secondary esophageal varices with bleeding |
| I864 | Gastric varices |
| K7040 | Alcoholic hepatic failure without coma |
| K7041 | Alcoholic hepatic failure with coma |
| K7210 | Chronic hepatic failure without coma |
| K7211 | Chronic hepatic failure with coma |
| K7290 | Hepatic failure, unspecified without coma |
| K7291 | Hepatic failure, unspecified with coma |
| K765 | Hepatic veno-occlusive disease |
| K766 | Portal hypertension |
| K767 | Hepatorenal syndrome |
| K9182 | Postprocedural hepatic failure |
| Z944 | Liver transplant status |
ICD-10-CM=International Classification of Diseases, 10th Edition Clinical Modification
Supplementary Table 6.
Case definition based on Internation Classification for Diseases, Tenth Revision (ICD-10) codes for end-stage renal failure
| ICD-10-CM diagnosis for ESRD | ICD-10-CM code description |
|---|---|
| I120 | Hypertensive chronic kidney disease with stage 5 chronic kidney disease or end-stage renal disease |
| I1311 | Hypertensive heart and chronic kidney disease without heart failure, with stage 5 chronic kidney disease or end-stage renal disease |
| I132 | Hypertensive heart and chronic kidney disease with heart failure and with stage 5 chronic kidney disease, or end-stage renal disease |
| N184 | Chronic kidney disease, stage 4 (severe) |
| N185 | Chronic kidney disease, stage 5 |
| N186 | End-stage renal disease |
| Z4901 | Encounter for fitting and adjustment of extracorporeal dialysis catheter |
| Z4902 | Encounter for fitting and adjustment of peritoneal dialysis catheter |
| Z4931 | Encounter for adequacy testing for hemodialysis |
| Z4932 | Encounter for adequacy testing for peritoneal dialysis |
| Z9115 | Patient’s noncompliance with renal dialysis |
| Z940 | Kidney transplant status |
| Z992 | Dependence on renal dialysis |
ESRD=End-stage renal disease, ICD-10-CM=International Classification of Diseases, 10th Edition Clinical Modification
Supplementary Table 7.
Case definition based on Internation Classification for Diseases, Tenth Revision (ICD-10) codes for Human Immunodeficiency Virus (HIV)
| ICD-10-CM diagnosis for HIV | ICD-10-CM code description |
|---|---|
| B20 | HIV disease |
| O98711 | HIV disease complicating pregnancy, first trimester |
| O98712 | HIV disease complicating pregnancy, second trimester |
| O98713 | HIV disease complicating pregnancy, third trimester |
| O98719 | HIV disease complicating pregnancy, unspecified trimester |
| O9872 | HIV disease complicating childbirth |
| O9873 | HIV disease complicating the puerperium |
| Z21 | Asymptomatic HIV infection status |
HIV=Human immunodeficiency virus, ICD-10-CM=International Classification of Diseases, 10th Edition Clinical Modification
Supplementary Table 8.
Case definition based on Internation Classification for Diseases, Tenth Revision (ICD-10) codes for leukemias
| ICD-10-CM diagnosis of leukemia | ICD-10-CM code description |
|---|---|
| C9010 | Plasma cell leukemia not having achieved remission |
| C9011 | Plasma cell leukemia in remission |
| C9012 | Plasma cell leukemia in relapse |
| C9100 | Acute lymphoblastic leukemia not having achieved remission |
| C9101 | Acute lymphoblastic leukemia, in remission |
| C9102 | Acute lymphoblastic leukemia, in relapse |
| C9110 | Chronic lymphocytic leukemia of B-cell type not having achieved remission |
| C9111 | Chronic lymphocytic leukemia of B-cell type in remission |
| C9112 | Chronic lymphocytic leukemia of B-cell type in relapse |
| C9130 | Prolymphocytic leukemia of B-cell type not having achieved remission |
| C9131 | Prolymphocytic leukemia of B-cell type, in remission |
| C9132 | Prolymphocytic leukemia of B-cell type, in relapse |
| C9140 | Hairy cell leukemia not having achieved remission |
| C9141 | Hairy cell leukemia, in remission |
| C9142 | Hairy cell leukemia, in relapse |
| C9150 | Adult T-cell lymphoma/leukemia (HTLV-1-associated) not having achieved remission |
| C9151 | Adult T-cell lymphoma/leukemia (HTLV-1-associated), in remission |
| C9152 | Adult T-cell lymphoma/leukemia (HTLV-1-associated), in relapse |
| C9160 | Prolymphocytic leukemia of T-cell type not having achieved remission |
| C9161 | Prolymphocytic leukemia of T-cell type, in remission |
| C9162 | Prolymphocytic leukemia of T-cell type, in relapse |
| C9190 | Lymphoid leukemia, unspecified not having achieved remission |
| C9191 | Lymphoid leukemia, unspecified, in remission |
| C9192 | Lymphoid leukemia, unspecified, in relapse |
| C91A0 | Mature B-cell leukemia Burkitt-type not having achieved remission |
| C91A1 | Mature B-cell leukemia Burkitt-type, in remission |
| C91A2 | Mature B-cell leukemia Burkitt-type, in relapse |
| C91Z0 | Other lymphoid leukemia not having achieved remission |
| C91Z1 | Other lymphoid leukemia, in remission |
| C91Z2 | Other lymphoid leukemia, in relapse |
| C9200 | Acute myeloblastic leukemia, not having achieved remission |
| C9201 | Acute myeloblastic leukemia, in remission |
| C9202 | Acute myeloblastic leukemia, in relapse |
| C9210 | Chronic myeloid leukemia, BCR/ABL - positive, not having achieved remission |
| C9211 | Chronic myeloid leukemia, BCR/ABL - positive, in remission |
| C9212 | Chronic myeloid leukemia, BCR/ABL - positive, in relapse |
| C9220 | Atypical chronic myeloid leukemia, BCR/ABL - negative, not having achieved remission |
| C9221 | Atypical chronic myeloid leukemia, BCR/ABL - negative, in remission |
| C9222 | Atypical chronic myeloid leukemia, BCR/ABL - negative, in relapse |
| C9230 | Myeloid sarcoma, not having achieved remission |
| C9231 | Myeloid sarcoma, in remission |
| C9232 | Myeloid sarcoma, in relapse |
| C9240 | Acute promyelocytic leukemia, not having achieved remission |
| C9241 | Acute promyelocytic leukemia, in remission |
| C9242 | Acute promyelocytic leukemia, in relapse |
| C9250 | Acute myelomonocytic leukemia, not having achieved remission |
| C9251 | Acute myelomonocytic leukemia, in remission |
| C9252 | Acute myelomonocytic leukemia, in relapse |
| C9260 | Acute myeloid leukemia with 11q23-abnormality not having achieved remission |
| C9261 | Acute myeloid leukemia with 11q23-abnormality in remission |
| C9262 | Acute myeloid leukemia with 11q23-abnormality in relapse |
| C9290 | Myeloid leukemia, unspecified, not having achieved remission |
| C9291 | Myeloid leukemia, unspecified in remission |
| C9292 | Myeloid leukemia, unspecified in relapse |
| C92A0 | Acute myeloid leukemia with multilineage dysplasia, not having achieved remission |
| C92A1 | Acute myeloid leukemia with multilineage dysplasia, in remission |
| C92A2 | Acute myeloid leukemia with multilineage dysplasia, in relapse |
| C92Z0 | Other myeloid leukemia not having achieved remission |
| C92Z1 | Other myeloid leukemia, in remission |
| C92Z2 | Other myeloid leukemia, in relapse |
| C9300 | Acute monoblastic/monocytic leukemia, not having achieved remission |
| C9301 | Acute monoblastic/monocytic leukemia, in remission |
| C9302 | Acute monoblastic/monocytic leukemia, in relapse |
| C9310 | Chronic myelomonocytic leukemia not having achieved remission |
| C9311 | Chronic myelomonocytic leukemia, in remission |
| C9312 | Chronic myelomonocytic leukemia, in relapse |
| C9330 | Juvenile myelomonocytic leukemia, not having achieved remission |
| C9331 | Juvenile myelomonocytic leukemia, in remission |
| C9332 | Juvenile myelomonocytic leukemia, in relapse |
| C9390 | Monocytic leukemia, unspecified, not having achieved remission |
| C9391 | Monocytic leukemia, unspecified in remission |
| C9392 | Monocytic leukemia, unspecified in relapse |
| C93Z0 | Other monocytic leukemia, not having achieved remission |
| C93Z1 | Other monocytic leukemia, in remission |
| C93Z2 | Other monocytic leukemia, in relapse |
| C9400 | Acute erythroid leukemia, not having achieved remission |
| C9401 | Acute erythroid leukemia, in remission |
| C9402 | Acute erythroid leukemia, in relapse |
| C9420 | Acute megakaryoblastic leukemia not having achieved remission |
| C9421 | Acute megakaryoblastic leukemia, in remission |
| C9422 | Acute megakaryoblastic leukemia, in relapse |
| C9430 | Mast cell leukemia not having achieved remission |
| C9431 | Mast cell leukemia, in remission |
| C9432 | Mast cell leukemia, in relapse |
| C9440 | Acute panmyelosis with myelofibrosis not having achieved remission |
| C9441 | Acute panmyelosis with myelofibrosis, in remission |
| C9442 | Acute panmyelosis with myelofibrosis, in relapse |
| C946 | Myelodysplastic disease, not classified |
| C9480 | Other specified leukemias not having achieved remission |
| C9481 | Other specified leukemias, in remission |
| C9482 | Other specified leukemias, in relapse |
| C9500 | Acute leukemia of unspecified cell type not having achieved remission |
| C9501 | Acute leukemia of unspecified cell type, in remission |
| C9502 | Acute leukemia of unspecified cell type, in relapse |
| C9510 | Chronic leukemia of unspecified cell type not having achieved remission |
| C9511 | Chronic leukemia of unspecified cell type, in remission |
| C9512 | Chronic leukemia of unspecified cell type, in relapse |
| C9590 | Leukemia, unspecified not having achieved remission |
| C9591 | Leukemia, unspecified, in remission |
| C9592 | Leukemia, unspecified, in relapse |
HTLV-1=Human T-cell leukemia/lymphotropic virus type 1, ICD-10-CM=International Classification of Diseases, 10th Edition Clinical Modification
Supplementary Table 9.
Case definition based on Internation Classification for Diseases, Tenth Revision (ICD-10) codes for lymphomas
| ICD-10-CM diagnosis of lymphoma | ICD-10-CM code description |
|---|---|
| C8100 | Nodular lymphocyte predominant Hodgkin’s lymphoma, unspecified site |
| C8101 | Nodular lymphocyte predominant Hodgkin’s lymphoma, lymph nodes of head, face, and neck |
| C8102 | Nodular lymphocyte predominant Hodgkin’s lymphoma, intrathoracic lymph nodes |
| C8103 | Nodular lymphocyte predominant Hodgkin’s lymphoma, intra-abdominal lymph nodes |
| C8104 | Nodular lymphocyte predominant Hodgkin’s lymphoma, lymph nodes of axilla and upper limb |
| C8105 | Nodular lymphocyte predominant Hodgkin’s lymphoma, lymph nodes of inguinal region and lower limb |
| C8106 | Nodular lymphocyte predominant Hodgkin’s lymphoma, intrapelvic lymph nodes |
| C8107 | Nodular lymphocyte predominant Hodgkin’s lymphoma, spleen |
| C8108 | Nodular lymphocyte predominant Hodgkin’s lymphoma, lymph nodes of multiple sites |
| C8109 | Nodular lymphocyte predominant Hodgkin’s lymphoma, extranodal and solid organ sites |
| C8110 | Nodular sclerosis Hodgkin’s lymphoma, unspecified site |
| C8111 | Nodular sclerosis Hodgkin’s lymphoma, lymph nodes of head, face, and neck |
| C8112 | Nodular sclerosis Hodgkin’s lymphoma, intrathoracic lymph nodes |
| C8113 | Nodular sclerosis Hodgkin’s lymphoma, intra-abdominal lymph nodes |
| C8114 | Nodular sclerosis Hodgkin’s lymphoma, lymph nodes of axilla and upper limb |
| C8115 | Nodular sclerosis Hodgkin’s lymphoma, lymph nodes of inguinal region and lower limb |
| C8116 | Nodular sclerosis Hodgkin’s lymphoma, intrapelvic lymph nodes |
| C8117 | Nodular sclerosis Hodgkin’s lymphoma, spleen |
| C8118 | Nodular sclerosis Hodgkin’s lymphoma, lymph nodes of multiple sites |
| C8119 | Nodular sclerosis Hodgkin’s lymphoma, extranodal and solid organ sites |
| C8120 | Mixed cellularity Hodgkin’s lymphoma, unspecified site |
| C8121 | Mixed cellularity Hodgkin’s lymphoma, lymph nodes of head, face, and neck |
| C8122 | Mixed cellularity Hodgkin’s lymphoma, intrathoracic lymph nodes |
| C8123 | Mixed cellularity Hodgkin’s lymphoma, intra-abdominal lymph nodes |
| C8124 | Mixed cellularity Hodgkin’s lymphoma, lymph nodes of axilla and upper limb |
| C8125 | Mixed cellularity Hodgkin’s lymphoma, lymph nodes of inguinal region and lower limb |
| C8126 | Mixed cellularity Hodgkin’s lymphoma, intrapelvic lymph nodes |
| C8127 | Mixed cellularity Hodgkin’s lymphoma, spleen |
| C8128 | Mixed cellularity Hodgkin’s lymphoma, lymph nodes of multiple sites |
| C8129 | Mixed cellularity Hodgkin’s lymphoma, extranodal and solid organ sites |
| C8130 | Lymphocyte-depleted Hodgkin’s lymphoma, unspecified site |
| C8131 | Lymphocyte-depleted Hodgkin’s lymphoma, lymph nodes of head, face, and neck |
| C8132 | Lymphocyte depleted Hodgkin’s lymphoma, intrathoracic lymph nodes |
| C8133 | Lymphocyte depleted Hodgkin’s lymphoma, intra-abdominal lymph nodes |
| C8134 | Lymphocyte-depleted Hodgkin’s lymphoma, lymph nodes of axilla and upper limb |
| C8135 | Lymphocyte-depleted Hodgkin’s lymphoma, lymph nodes of inguinal region and lower limb |
| C8136 | Lymphocyte-depleted Hodgkin’s lymphoma, intrapelvic lymph nodes |
| C8137 | Lymphocyte-depleted Hodgkin’s lymphoma, spleen |
| C8138 | Lymphocyte-depleted Hodgkin’ lymphoma, lymph nodes of multiple sites |
| C8139 | Lymphocyte-depleted Hodgkin’s lymphoma, extranodal and solid organ sites |
| C8140 | Lymphocyte-rich Hodgkin’s lymphoma, unspecified site |
| C8141 | Lymphocyte-rich Hodgkin’s lymphoma, lymph nodes of head, face, and neck |
| C8142 | Lymphocyte-rich Hodgkin’s lymphoma, intrathoracic lymph nodes |
| C8143 | Lymphocyte-rich Hodgkin’s lymphoma, intra-abdominal lymph nodes |
| C8144 | Lymphocyte-rich Hodgkin’s lymphoma, lymph nodes of axilla and upper limb |
| C8145 | Lymphocyte-rich Hodgkin’s lymphoma, lymph nodes of inguinal region and lower limb |
| C8146 | Lymphocyte-rich Hodgkin’s lymphoma, intrapelvic lymph nodes |
| C8147 | Lymphocyte-rich Hodgkin’s lymphoma, spleen |
| C8148 | Lymphocyte-rich Hodgkin’s lymphoma, lymph nodes of multiple sites |
| C8149 | Lymphocyte-rich Hodgkin’s lymphoma, extranodal and solid organ sites |
| C8170 | Other Hodgkin’s lymphoma, unspecified site |
| C8171 | Other Hodgkin’s lymphoma, lymph nodes of head, face, and neck |
| C8172 | Other Hodgkin’s lymphoma, intrathoracic lymph nodes |
| C8173 | Other Hodgkin’s lymphoma, intra-abdominal lymph nodes |
| C8174 | Other Hodgkin’s lymphoma, lymph nodes of axilla and upper limb |
| C8175 | Other Hodgkin’s lymphoma, lymph nodes of inguinal region and lower limb |
| C8176 | Other Hodgkin’s lymphoma, intrapelvic lymph nodes |
| C8177 | Other Hodgkin’s lymphoma, spleen |
| C8178 | Other Hodgkin’s lymphoma, lymph nodes of multiple sites |
| C8179 | Other Hodgkin’s lymphoma, extranodal and solid organ sites |
| C8190 | Hodgkin’s lymphoma, unspecified, unspecified site |
| C8191 | Hodgkin’s lymphoma, unspecified, lymph nodes of head, face, and neck |
| C8192 | Hodgkin’s lymphoma, unspecified, intrathoracic lymph nodes |
| C8193 | Hodgkin’s lymphoma, unspecified, intra-abdominal lymph nodes |
| C8194 | Hodgkin’s lymphoma, unspecified, lymph nodes of axilla and upper limb |
| C8195 | Hodgkin’s lymphoma, unspecified, lymph nodes of inguinal region and lower limb |
| C8196 | Hodgkin’s lymphoma, unspecified, intrapelvic lymph nodes |
| C8197 | Hodgkin’s lymphoma, unspecified, spleen |
| C8198 | Hodgkin’s lymphoma, unspecified, lymph nodes of multiple sites |
| C8199 | Hodgkin’s lymphoma, unspecified, extranodal and solid organ sites |
| C8200 | Follicular lymphoma grade I, unspecified site |
| C8201 | Follicular lymphoma grade I, lymph nodes of head, face and neck |
| C8202 | Follicular lymphoma grade I, intrathoracic lymph nodes |
| C8203 | Follicular lymphoma grade I, intra-abdominal lymph nodes |
| C8204 | Follicular lymphoma grade I, lymph nodes of axilla and upper limb |
| C8205 | Follicular lymphoma grade I, lymph nodes of inguinal region and lower limb |
| C8206 | Follicular lymphoma grade I, intrapelvic lymph nodes |
| C8207 | Follicular lymphoma grade I, spleen |
| C8208 | Follicular lymphoma grade I, lymph nodes of multiple sites |
| C8209 | Follicular lymphoma grade I, extranodal and solid organ sites |
| C8210 | Follicular lymphoma grade II, unspecified site |
| C8211 | Follicular lymphoma grade II, lymph nodes of head, face and neck |
| C8212 | Follicular lymphoma grade II, intrathoracic lymph nodes |
| C8213 | Follicular lymphoma grade II, intra-abdominal lymph nodes |
| C8214 | Follicular lymphoma grade II, lymph nodes of axilla and upper limb |
| C8215 | Follicular lymphoma grade II, lymph nodes of inguinal region and lower limb |
| C8216 | Follicular lymphoma grade II, intrapelvic lymph nodes |
| C8217 | Follicular lymphoma grade II, spleen |
| C8218 | Follicular lymphoma grade II, lymph nodes of multiple sites |
| C8219 | Follicular lymphoma grade II, extranodal and solid organ sites |
| C8220 | Follicular lymphoma grade III, unspecified, unspecified site |
| C8221 | Follicular lymphoma grade III, unspecified, lymph nodes of head, face and neck |
| C8222 | Follicular lymphoma grade III, unspecified, intrathoracic lymph nodes |
| C8223 | Follicular lymphoma grade III, unspecified, intra-abdominal lymph nodes |
| C8224 | Follicular lymphoma grade III, unspecified, lymph nodes of axilla and upper limb |
| C8225 | Follicular lymphoma grade III, unspecified, lymph nodes of inguinal region and lower limb |
| C8226 | Follicular lymphoma grade III, unspecified, intrapelvic lymph nodes |
| C8227 | Follicular lymphoma grade III, unspecified, spleen |
| C8228 | Follicular lymphoma grade III, unspecified, lymph nodes of multiple sites |
| C8229 | Follicular lymphoma grade III, unspecified, extranodal and solid organ sites |
| C8230 | Follicular lymphoma grade IIIa, unspecified site |
| C8231 | Follicular lymphoma grade IIIa, lymph nodes of head, face and neck |
| C8232 | Follicular lymphoma grade IIIa, intrathoracic lymph nodes |
| C8233 | Follicular lymphoma grade IIIa, intra-abdominal lymph nodes |
| C8234 | Follicular lymphoma grade IIIa, lymph nodes of axilla and upper limb |
| C8235 | Follicular lymphoma grade IIIa, lymph nodes of inguinal region and lower limb |
| C8236 | Follicular lymphoma grade IIIa, intrapelvic lymph nodes |
| C8237 | Follicular lymphoma grade IIIa, spleen |
| C8238 | Follicular lymphoma grade IIIa, lymph nodes of multiple sites |
| C8239 | Follicular lymphoma grade IIIa, extranodal and solid organ sites |
| C8240 | Follicular lymphoma grade IIIb, unspecified site |
| C8241 | Follicular lymphoma grade IIIb, lymph nodes of head, face, and neck |
| C8242 | Follicular lymphoma grade IIIb, intrathoracic lymph nodes |
| C8243 | Follicular lymphoma grade IIIb, intra-abdominal lymph nodes |
| C8244 | Follicular lymphoma grade IIIb, lymph nodes of axilla and upper limb |
| C8245 | Follicular lymphoma grade IIIb, lymph nodes of inguinal region and lower limb |
| C8246 | Follicular lymphoma grade IIIb, intrapelvic lymph nodes |
| C8247 | Follicular lymphoma grade IIIb, spleen |
| C8248 | Follicular lymphoma grade IIIb, lymph nodes of multiple sites |
| C8249 | Follicular lymphoma grade IIIb, extranodal and solid organ sites |
| C8250 | Diffuse follicle center lymphoma, unspecified site |
| C8251 | Diffuse follicle center lymphoma, lymph nodes of head, face and neck |
| C8252 | Diffuse follicle center lymphoma, intrathoracic lymph nodes |
| C8253 | Diffuse follicle center lymphoma, intra-abdominal lymph nodes |
| C8254 | Diffuse follicle center lymphoma, lymph nodes of axilla and upper limb |
| C8255 | Diffuse follicle center lymphoma, lymph nodes of inguinal region and lower limb |
| C8256 | Diffuse follicle center lymphoma, intrapelvic lymph nodes |
| C8257 | Diffuse follicle center lymphoma, spleen |
| C8258 | Diffuse follicle center lymphoma, lymph nodes of multiple sites |
| C8259 | Diffuse follicle center lymphoma, extranodal and solid organ sites |
| C8260 | Cutaneous follicle center lymphoma, unspecified site |
| C8261 | Cutaneous follicle center lymphoma, lymph nodes of head, face and neck |
| C8262 | Cutaneous follicle center lymphoma, intrathoracic lymph nodes |
| C8263 | Cutaneous follicle center lymphoma, intra-abdominal lymph nodes |
| C8264 | Cutaneous follicle center lymphoma, lymph nodes of axilla and upper limb |
| C8265 | Cutaneous follicle center lymphoma, lymph nodes of inguinal region and lower limb |
| C8266 | Cutaneous follicle center lymphoma, intrapelvic lymph nodes |
| C8267 | Cutaneous follicle center lymphoma, spleen |
| C8268 | Cutaneous follicle center lymphoma, lymph nodes of multiple sites |
| C8269 | Cutaneous follicle center lymphoma, extranodal and solid organ sites |
| C8280 | Other types of follicular lymphoma, unspecified site |
| C8281 | Other types of follicular lymphoma, lymph nodes of head, face and neck |
| C8282 | Other types of follicular lymphoma, intrathoracic lymph nodes |
| C8283 | Other types of follicular lymphoma, intra-abdominal lymph nodes |
| C8284 | Other types of follicular lymphoma, lymph nodes of axilla and upper limb |
| C8285 | Other types of follicular lymphoma, lymph nodes of inguinal region and lower limb |
| C8286 | Other types of follicular lymphoma, intrapelvic lymph nodes |
| C8287 | Other types of follicular lymphoma, spleen |
| C8288 | Other types of follicular lymphoma, lymph nodes of multiple sites |
| C8289 | Other types of follicular lymphoma, extranodal and solid organ sites |
| C8290 | Follicular lymphoma, unspecified, unspecified site |
| C8291 | Follicular lymphoma, unspecified, lymph nodes of head, face and neck |
| C8292 | Follicular lymphoma, unspecified, intrathoracic lymph nodes |
| C8293 | Follicular lymphoma, unspecified, intra-abdominal lymph nodes |
| C8294 | Follicular lymphoma, unspecified, lymph nodes of axilla and upper limb |
| C8295 | Follicular lymphoma, unspecified, lymph nodes of inguinal region and lower limb |
| C8296 | Follicular lymphoma, unspecified, intrapelvic lymph nodes |
| C8297 | Follicular lymphoma, unspecified, spleen |
| C8298 | Follicular lymphoma, unspecified, lymph nodes of multiple sites |
| C8299 | Follicular lymphoma, unspecified, extranodal and solid organ sites |
| C8300 | Small cell B-cell lymphoma, unspecified site |
| C8301 | Small cell B-cell lymphoma, lymph nodes of head, face and neck |
| C8302 | Small cell B-cell lymphoma, intrathoracic lymph nodes |
| C8303 | Small cell B-cell lymphoma, intra-abdominal lymph nodes |
| C8304 | Small cell B-cell lymphoma, lymph nodes of axilla and upper limb |
| C8305 | Small cell B-cell lymphoma, lymph nodes of inguinal region and lower limb |
| C8306 | Small cell B-cell lymphoma, intrapelvic lymph nodes |
| C8307 | Small cell B-cell lymphoma, spleen |
| C8308 | Small cell B-cell lymphoma, lymph nodes of multiple sites |
| C8309 | Small cell B-cell lymphoma, extranodal and solid organ sites |
| C8310 | Mantle cell lymphoma, unspecified site |
| C8311 | Mantle cell lymphoma, lymph nodes of head, face and neck |
| C8312 | Mantle cell lymphoma, intrathoracic lymph nodes |
| C8313 | Mantle cell lymphoma, intra-abdominal lymph nodes |
| C8314 | Mantle cell lymphoma, lymph nodes of axilla and upper limb |
| C8315 | Mantle cell lymphoma, lymph nodes of inguinal region and lower limb |
| C8316 | Mantle cell lymphoma, intrapelvic lymph nodes |
| C8317 | Mantle cell lymphoma, spleen |
| C8318 | Mantle cell lymphoma, lymph nodes of multiple sites |
| C8319 | Mantle cell lymphoma, extranodal and solid organ sites |
| C8330 | Diffuse large B-cell lymphoma, unspecified site |
| C8331 | Diffuse large B-cell lymphoma, lymph nodes of head, face and neck |
| C8332 | Diffuse large B-cell lymphoma, intrathoracic lymph nodes |
| C8333 | Diffuse large B-cell lymphoma, intra-abdominal lymph nodes |
| C8334 | Diffuse large B-cell lymphoma, lymph nodes of axilla and upper limb |
| C8335 | Diffuse large B-cell lymphoma, lymph nodes of inguinal region and lower limb |
| C8336 | Diffuse large B-cell lymphoma, intrapelvic lymph nodes |
| C8337 | Diffuse large B-cell lymphoma, spleen |
| C8338 | Diffuse large B-cell lymphoma, lymph nodes of multiple sites |
| C8339 | Diffuse large B-cell lymphoma, extranodal and solid organ sites |
| C8350 | Lymphoblastic (diffuse) lymphoma, unspecified site |
| C8351 | Lymphoblastic (diffuse) lymphoma, lymph nodes of head, face and neck |
| C8352 | Lymphoblastic (diffuse) lymphoma, intrathoracic lymph nodes |
| C8353 | Lymphoblastic (diffuse) lymphoma, intra-abdominal lymph nodes |
| C8354 | Lymphoblastic (diffuse) lymphoma, lymph nodes of axilla and upper limb |
| C8355 | Lymphoblastic (diffuse) lymphoma, lymph nodes of inguinal region and lower limb |
| C8356 | Lymphoblastic (diffuse) lymphoma, intrapelvic lymph nodes |
| C8357 | Lymphoblastic (diffuse) lymphoma, spleen |
| C8358 | Lymphoblastic (diffuse) lymphoma, lymph nodes of multiple sites |
| C8359 | Lymphoblastic (diffuse) lymphoma, extranodal and solid organ sites |
| C8370 | Burkitt lymphoma, unspecified site |
| C8371 | Burkitt lymphoma, lymph nodes of head, face and neck |
| C8372 | Burkitt lymphoma, intrathoracic lymph nodes |
| C8373 | Burkitt lymphoma, intra-abdominal lymph nodes |
| C8374 | Burkitt lymphoma, lymph nodes of axilla and upper limb |
| C8375 | Burkitt lymphoma, lymph nodes of inguinal region and lower limb |
| C8376 | Burkitt lymphoma, intrapelvic lymph nodes |
| C8377 | Burkitt lymphoma, spleen |
| C8378 | Burkitt lymphoma, lymph nodes of multiple sites |
| C8379 | Burkitt lymphoma, extranodal and solid organ sites |
| C8380 | Other nonfollicular lymphoma, unspecified site |
| C8381 | Other nonfollicular lymphoma, lymph nodes of head, face and neck |
| C8382 | Other nonfollicular lymphoma, intrathoracic lymph nodes |
| C8383 | Other nonfollicular lymphoma, intra-abdominal lymph nodes |
| C8384 | Other nonfollicular lymphoma, lymph nodes of axilla and upper limb |
| C8385 | Other nonfollicular lymphoma, lymph nodes of inguinal region and lower limb |
| C8386 | Other nonfollicular lymphoma, intrapelvic lymph nodes |
| C8387 | Other nonfollicular lymphoma, spleen |
| C8388 | Other nonfollicular lymphoma, lymph nodes of multiple sites |
| C8389 | Other nonfollicular lymphoma, extranodal and solid organ sites |
| C8390 | Nonfollicular (diffuse) lymphoma, unspecified, unspecified site |
| C8391 | Nonfollicular (diffuse) lymphoma, unspecified, lymph nodes of head, face and neck |
| C8392 | Nonfollicular (diffuse) lymphoma, unspecified, intrathoracic lymph nodes |
| C8393 | Nonfollicular (diffuse) lymphoma, unspecified, intra-abdominal lymph nodes |
| C8394 | Nonfollicular (diffuse) lymphoma, unspecified, lymph nodes of axilla and upper limb |
| C8395 | Nonfollicular (diffuse) lymphoma, unspecified, lymph nodes of inguinal region and lower limb |
| C8396 | Nonfollicular (diffuse) lymphoma, unspecified, intrapelvic lymph nodes |
| C8397 | Nonfollicular (diffuse) lymphoma, unspecified, spleen |
| C8398 | Nonfollicular (diffuse) lymphoma, unspecified, lymph nodes of multiple sites |
| C8399 | Nonfollicular (diffuse) lymphoma, unspecified, extranodal and solid organ sites |
| C8400 | Mycosis fungoides, unspecified site |
| C8401 | Mycosis fungoides, lymph nodes of head, face and neck |
| C8402 | Mycosis fungoides, intrathoracic lymph nodes |
| C8403 | Mycosis fungoides, intra-abdominal lymph nodes |
| C8404 | Mycosis fungoides, lymph nodes of axilla and upper limb |
| C8405 | Mycosis fungoides, lymph nodes of inguinal region and lower limb |
| C8406 | Mycosis fungoides, intrapelvic lymph nodes |
| C8407 | Mycosis fungoides, spleen |
| C8408 | Mycosis fungoides, lymph nodes of multiple sites |
| C8409 | Mycosis fungoides, extranodal and solid organ sites |
| C8410 | Sezary disease, unspecified site |
| C8411 | Sezary disease, lymph nodes of head, face and neck |
| C8412 | Sezary disease, intrathoracic lymph nodes |
| C8413 | Sezary disease, intra-abdominal lymph nodes |
| C8414 | Sezary disease, lymph nodes of axilla and upper limb |
| C8415 | Sezary disease, lymph nodes of inguinal region and lower limb |
| C8416 | Sezary disease, intrapelvic lymph nodes |
| C8417 | Sezary disease, spleen |
| C8418 | Sezary disease, lymph nodes of multiple sites |
| C8419 | Sezary disease, extranodal and solid organ sites |
| C8440 | Peripheral T-cell lymphoma, not classified, unspecified site |
| C8441 | Peripheral T-cell lymphoma, not classified, lymph nodes of head, face and neck |
| C8442 | Peripheral T-cell lymphoma, not classified, intrathoracic lymph nodes |
| C8443 | Peripheral T-cell lymphoma, not classified, intra-abdominal lymph nodes |
| C8444 | Peripheral T-cell lymphoma, not classified, lymph nodes of axilla and upper limb |
| C8445 | Peripheral T-cell lymphoma, not classified, lymph nodes of inguinal region and lower limb |
| C8446 | Peripheral T-cell lymphoma, not classified, intrapelvic lymph nodes |
| C8447 | Peripheral T-cell lymphoma, not classified, spleen |
| C8448 | Peripheral T-cell lymphoma, not classified, lymph nodes of multiple sites |
| C8449 | Peripheral T-cell lymphoma, not classified, extranodal and solid organ sites |
| C8460 | Anaplastic large cell lymphoma, ALK-positive, unspecified site |
| C8461 | Anaplastic large cell lymphoma, ALK-positive, lymph nodes of head, face and neck |
| C8462 | Anaplastic large cell lymphoma, ALK-positive, intrathoracic lymph nodes |
| C8463 | Anaplastic large cell lymphoma, ALK-positive, intra-abdominal lymph nodes |
| C8464 | Anaplastic large cell lymphoma, ALK-positive, lymph nodes of axilla and upper limb |
| C8465 | Anaplastic large cell lymphoma, ALK-positive, lymph nodes of inguinal region and lower limb |
| C8466 | Anaplastic large cell lymphoma, ALK-positive, intrapelvic lymph nodes |
| C8467 | Anaplastic large cell lymphoma, ALK-positive, spleen |
| C8468 | Anaplastic large cell lymphoma, ALK-positive, lymph nodes of multiple sites |
| C8469 | Anaplastic large cell lymphoma, ALK-positive, extranodal and solid organ sites |
| C8470 | Anaplastic large cell lymphoma, ALK-negative, unspecified site |
| C8471 | Anaplastic large cell lymphoma, ALK-negative, lymph nodes of head, face and neck |
| C8472 | Anaplastic large cell lymphoma, ALK-negative, intrathoracic lymph nodes |
| C8473 | Anaplastic large cell lymphoma, ALK-negative, intra-abdominal lymph nodes |
| C8474 | Anaplastic large cell lymphoma, ALK-negative, lymph nodes of axilla and upper limb |
| C8475 | Anaplastic large cell lymphoma, ALK-negative, lymph nodes of inguinal region and lower limb |
| C8476 | Anaplastic large cell lymphoma, ALK-negative, intrapelvic lymph nodes |
| C8477 | Anaplastic large cell lymphoma, ALK-negative, spleen |
| C8478 | Anaplastic large cell lymphoma, ALK-negative, lymph nodes of multiple sites |
| C8479 | Anaplastic large cell lymphoma, ALK-negative, extranodal and solid organ sites |
| C847A | Anaplastic large cell lymphoma, ALK-negative, breast |
| C8490 | Mature T/NK-cell lymphomas, unspecified, unspecified site |
| C8491 | Mature T/NK-cell lymphomas, unspecified, lymph nodes of head, face and neck |
| C8492 | Mature T/NK-cell lymphomas, unspecified, intrathoracic lymph nodes |
| C8493 | Mature T/NK-cell lymphomas, unspecified, intra-abdominal lymph nodes |
| C8494 | Mature T/NK-cell lymphomas, unspecified, lymph nodes of axilla and upper limb |
| C8495 | Mature T/NK-cell lymphomas, unspecified, lymph nodes of inguinal region and lower limb |
| C8496 | Mature T/NK-cell lymphomas, unspecified, intrapelvic lymph nodes |
| C8497 | Mature T/NK-cell lymphomas, unspecified, spleen |
| C8498 | Mature T/NK-cell lymphomas, unspecified, lymph nodes of multiple sites |
| C8499 | Mature T/NK-cell lymphomas, unspecified, extranodal and solid organ sites |
| C84A0 | Cutaneous T-cell lymphoma, unspecified, unspecified site |
| C84A1 | Cutaneous T-cell lymphoma, unspecified lymph nodes of head, face and neck |
| C84A2 | Cutaneous T-cell lymphoma, unspecified, intrathoracic lymph nodes |
| C84A3 | Cutaneous T-cell lymphoma, unspecified, intra-abdominal lymph nodes |
| C84A4 | Cutaneous T-cell lymphoma, unspecified, lymph nodes of axilla and upper limb |
| C84A5 | Cutaneous T-cell lymphoma, unspecified, lymph nodes of inguinal region and lower limb |
| C84A6 | Cutaneous T-cell lymphoma, unspecified, intrapelvic lymph nodes |
| C84A7 | Cutaneous T-cell lymphoma, unspecified, spleen |
| C84A8 | Cutaneous T-cell lymphoma, unspecified, lymph nodes of multiple sites |
| C84A9 | Cutaneous T-cell lymphoma, unspecified, extranodal and solid organ sites |
| C84Z0 | Other mature T/NK-cell lymphomas, unspecified site |
| C84Z1 | Other mature T/NK-cell lymphomas, lymph nodes of head, face and neck |
| C84Z2 | Other mature T/NK-cell lymphomas, intrathoracic lymph nodes |
| C84Z3 | Other mature T/NK-cell lymphomas, intra-abdominal lymph nodes |
| C84Z4 | Other mature T/NK-cell lymphomas, lymph nodes of axilla and upper limb |
| C84Z5 | Other mature T/NK-cell lymphomas, lymph nodes of inguinal region and lower limb |
| C84Z6 | Other mature T/NK-cell lymphomas, intrapelvic lymph nodes |
| C84Z7 | Other mature T/NK-cell lymphomas, spleen |
| C84Z8 | Other mature T/NK-cell lymphomas, lymph nodes of multiple sites |
| C84Z9 | Other mature T/NK-cell lymphomas, extranodal and solid organ sites |
| C8510 | Unspecified B-cell lymphoma, unspecified site |
| C8511 | Unspecified B-cell lymphoma, lymph nodes of head, face and neck |
| C8512 | Unspecified B-cell lymphoma, intrathoracic lymph nodes |
| C8513 | Unspecified B-cell lymphoma, intra-abdominal lymph nodes |
| C8514 | Unspecified B-cell lymphoma, lymph nodes of axilla and upper limb |
| C8515 | Unspecified B-cell lymphoma, lymph nodes of inguinal region and lower limb |
| C8516 | Unspecified B-cell lymphoma, intrapelvic lymph nodes |
| C8517 | Unspecified B-cell lymphoma, spleen |
| C8518 | Unspecified B-cell lymphoma, lymph nodes of multiple sites |
| C8519 | Unspecified B-cell lymphoma, extranodal and solid organ sites |
| C8520 | Mediastinal (thymic) large B-cell lymphoma, unspecified site |
| C8521 | Mediastinal (thymic) large B-cell lymphoma, lymph nodes of head, face and neck |
| C8522 | Mediastinal (thymic) large B-cell lymphoma, intrathoracic lymph nodes |
| C8523 | Mediastinal (thymic) large B-cell lymphoma, intra-abdominal lymph nodes |
| C8524 | Mediastinal (thymic) large B-cell lymphoma, lymph nodes of axilla and upper limb |
| C8525 | Mediastinal (thymic) large B-cell lymphoma, lymph nodes of inguinal region and lower limb |
| C8526 | Mediastinal (thymic) large B-cell lymphoma, intrapelvic lymph nodes |
| C8527 | Mediastinal (thymic) large B-cell lymphoma, spleen |
| C8528 | Mediastinal (thymic) large B-cell lymphoma, lymph nodes of multiple sites |
| C8529 | Mediastinal (thymic) large B-cell lymphoma, extranodal and solid organ sites |
| C8580 | Other specified types of non-Hodgkin’s lymphoma, unspecified site |
| C8581 | Other specified types of non-Hodgkin’s lymphoma, lymph nodes of head, face and neck |
| C8582 | Other specified types of non-Hodgkin’s lymphoma, intrathoracic lymph nodes |
| C8583 | Other specified types of non-Hodgkin’s lymphoma, intra-abdominal lymph nodes |
| C8584 | Other specified types of non-Hodgkin’s lymphoma, lymph nodes of axilla and upper limb |
| C8585 | Other specified types of non-Hodgkin’s lymphoma, lymph nodes of inguinal region and lower limb |
| C8586 | Other specified types of non-Hodgkin’s lymphoma, intrapelvic lymph nodes |
| C8587 | Other specified types of non-Hodgkin’s lymphoma, spleen |
| C8588 | Other specified types of non-Hodgkin’s lymphoma, lymph nodes of multiple sites |
| C8589 | Other specified types of non-Hodgkin’s lymphoma, extranodal and solid organ sites |
| C8590 | Non-Hodgkin’s lymphoma, unspecified, unspecified site |
| C8591 | Non-Hodgkin’s lymphoma, unspecified, lymph nodes of head, face, and neck |
| C8592 | Non-Hodgkin’s lymphoma, unspecified, intrathoracic lymph nodes |
| C8593 | Non-Hodgkin’s lymphoma, unspecified, intra-abdominal lymph nodes |
| C8594 | Non-Hodgkin’s lymphoma, unspecified, lymph nodes of axilla and upper limb |
| C8595 | Non-Hodgkin’s lymphoma, unspecified, lymph nodes of inguinal region and lower limb |
| C8596 | Non-Hodgkin’s lymphoma, unspecified, intrapelvic lymph nodes |
| C8597 | Non-Hodgkin’s lymphoma, unspecified, spleen |
| C8598 | Non-Hodgkin’s lymphoma, unspecified, lymph nodes of multiple sites |
| C8599 | Non-Hodgkin’s lymphoma, unspecified, extranodal and solid organ sites |
| C860 | Extranodal NK/T-cell lymphoma, nasal type |
| C861 | Hepatosplenic T-cell lymphoma |
| C862 | Enteropathy-type (intestinal) T-cell lymphoma |
| C863 | Subcutaneous panniculitis-like T-cell lymphoma |
| C864 | Blastic NK-cell lymphoma |
| C865 | Angioimmunoblastic T-cell lymphoma |
| C866 | Primary cutaneous CD30-positive T-cell proliferations |
| C880 | Waldenstrom macroglobulinemia |
| C882 | Heavy chain disease |
| C883 | Immunoproliferative small intestinal disease |
| C884 | Extranodal MALT-lymphoma |
| C888 | Other malignant immunoproliferative diseases |
| C889 | Malignant immunoproliferative disease, unspecified |
| C9000 | Multiple myeloma not having achieved remission |
| C9001 | Multiple myeloma in remission |
| C9002 | Multiple myeloma in relapse |
| C9020 | Extramedullary plasmacytoma not having achieved remission |
| C9021 | Extramedullary plasmacytoma in remission |
| C9022 | Extramedullary plasmacytoma in relapse |
| C9030 | Solitary plasmacytoma not having achieved remission |
| C9031 | Solitary plasmacytoma in remission |
| C9032 | Solitary plasmacytoma in relapse |
| C960 | Multifocal and multisystemic (disseminated) Langerhans-cell histiocytosis |
| C962 | Malignant mast cell tumor |
| C9620 | Malignant mast cell neoplasm, unspecified |
| C9621 | Aggressive systemic mastocytosis |
| C9622 | Mast cell sarcoma |
| C9629 | Other malignant mast cell neoplasm |
| C964 | Sarcoma of dendritic cells (accessory cells) |
| C969 | Malignant neoplasm of lymphoid, hematopoietic and related tissue, unspecified |
| C96A | Histiocytic sarcoma |
| C96Z | Other specified malignant neoplasms of lymphoid, hematopoietic, and related tissue |
| D47Z9 | Other specified neoplasms of uncertain behavior of lymphoid, hematopoietic, and related tissue |
MALT=Marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, NK=Natural killer, ALK=Anaplastic lymphoma kinase, ICD-10-CM=International Classification of Diseases, 10th Edition Clinical Modification
Supplementary Table 10.
Case definition based on Internation Classification for Diseases, Tenth Revision (ICD-10) codes for metastatic disease
| ICD-10-CM diagnosis of metastatic cancer | ICD-10-CM code description |
|---|---|
| C770 | Secondary and unspecified malignant neoplasm of lymph nodes of head, face and neck |
| C771 | Secondary and unspecified malignant neoplasm of intrathoracic lymph nodes |
| C772 | Secondary and unspecified malignant neoplasm of intra-abdominal lymph nodes |
| C773 | Secondary and unspecified malignant neoplasm of axilla and upper limb lymph nodes |
| C774 | Secondary and unspecified malignant neoplasm of inguinal and lower limb lymph nodes |
| C775 | Secondary and unspecified malignant neoplasm of intrapelvic lymph nodes |
| C778 | Secondary and unspecified malignant neoplasm of lymph nodes of multiple regions |
| C779 | Secondary and unspecified malignant neoplasm of lymph node, unspecified |
| C7800 | Secondary malignant neoplasm of unspecified lung |
| C7801 | Secondary malignant neoplasm of right lung |
| C7802 | Secondary malignant neoplasm of left lung |
| C781 | Secondary malignant neoplasm of mediastinum |
| C782 | Secondary malignant neoplasm of pleura |
| C7830 | Secondary malignant neoplasm of unspecified respiratory organ |
| C7839 | Secondary malignant neoplasm of other respiratory organs |
| C784 | Secondary malignant neoplasm of small intestine |
| C785 | Secondary malignant neoplasm of large intestine and rectum |
| C786 | Secondary malignant neoplasm of retroperitoneum and peritoneum |
| C787 | Secondary malignant neoplasm of liver and intrahepatic bile duct |
| C7880 | Secondary malignant neoplasm of unspecified digestive organ |
| C7889 | Secondary malignant neoplasm of other digestive organs |
| C7900 | Secondary malignant neoplasm of unspecified kidney and renal pelvis |
| C7901 | Secondary malignant neoplasm of right kidney and renal pelvis |
| C7902 | Secondary malignant neoplasm of left kidney and renal pelvis |
| C7910 | Secondary malignant neoplasm of unspecified urinary organs |
| C7911 | Secondary malignant neoplasm of bladder |
| C7919 | Secondary malignant neoplasm of other urinary organs |
| C792 | Secondary malignant neoplasm of skin |
| C7931 | Secondary malignant neoplasm of brain |
| C7932 | Secondary malignant neoplasm of cerebral meninges |
| C7940 | Secondary malignant neoplasm of unspecified part of nervous system |
| C7949 | Secondary malignant neoplasm of other parts of nervous system |
| C7951 | Secondary malignant neoplasm of bone |
| C7952 | Secondary malignant neoplasm of bone marrow |
| C7960 | Secondary malignant neoplasm of unspecified ovary |
| C7961 | Secondary malignant neoplasm of right ovary |
| C7962 | Secondary malignant neoplasm of left ovary |
| C7963 | Secondary malignant neoplasm of bilateral ovaries |
| C7970 | Secondary malignant neoplasm of unspecified adrenal gland |
| C7971 | Secondary malignant neoplasm of right adrenal gland |
| C7972 | Secondary malignant neoplasm of left adrenal gland |
| C7981 | Secondary malignant neoplasm of breast |
| C7982 | Secondary malignant neoplasm of genital organs |
| C7989 | Secondary malignant neoplasm of other specified sites |
| C799 | Secondary malignant neoplasm of unspecified site |
| C7B00 | Secondary carcinoid tumors, unspecified site |
| C7B01 | Secondary carcinoid tumors of distant lymph nodes |
| C7B02 | Secondary carcinoid tumors of liver |
| C7B03 | Secondary carcinoid tumors of bone |
| C7B04 | Secondary carcinoid tumors of peritoneum |
| C7B09 | Secondary carcinoid tumors of other sites |
| C7B1 | Secondary Merkel cell carcinoma |
| C7B8 | Other secondary neuroendocrine tumors |
| C800 | Disseminated malignant neoplasm, unspecified |
ICD-10-CM=International Classification of Diseases, 10th Edition Clinical Modification
Supplementary Table 11.
Case definition based on Internation Classification for Diseases, Tenth Revision (ICD-10) codes for carcinoma in situ
| ICD-10-CM diagnosis of carcinoma in situ | ICD-10-CM code description |
|---|---|
| D0000 | Carcinoma in situ of oral cavity, unspecified site |
| D0001 | Carcinoma in situ of labial mucosa and vermilion border |
| D0002 | Carcinoma in situ of buccal mucosa |
| D0003 | Carcinoma in situ of gingiva and edentulous alveolar ridge |
| D0004 | Carcinoma in situ of soft palate |
| D0005 | Carcinoma in situ of hard palate |
| D0006 | Carcinoma in situ of floor of mouth |
| D0007 | Carcinoma in situ of tongue |
| D0008 | Carcinoma in situ of pharynx |
| D001 | Carcinoma in situ of esophagus |
| D002 | Carcinoma in situ of stomach |
| D010 | Carcinoma in situ of colon |
| D011 | Carcinoma in situ of rectosigmoid junction |
| D012 | Carcinoma in situ of rectum |
| D013 | Carcinoma in situ of anus and anal canal |
| D0140 | Carcinoma in situ of unspecified part of intestine |
| D0149 | Carcinoma in situ of other parts of intestine |
| D015 | Carcinoma in situ of liver, gallbladder and bile ducts |
| D017 | Carcinoma in situ of other specified digestive organs |
| D019 | Carcinoma in situ of digestive organ, unspecified |
| D020 | Carcinoma in situ of larynx |
| D021 | Carcinoma in situ of trachea |
| D0220 | Carcinoma in situ of unspecified bronchus and lung |
| D0221 | Carcinoma in situ of right bronchus and lung |
| D0222 | Carcinoma in situ of left bronchus and lung |
| D023 | Carcinoma in situ of other parts of respiratory system |
| D024 | Carcinoma in situ of respiratory system, unspecified |
| D030 | Melanoma in situ of lip |
| D0310 | Melanoma in situ of unspecified eyelid, including canthus |
| D0311 | Melanoma in situ of right eyelid, including canthus |
| D03111 | Melanoma in situ of right upper eyelid, including canthus |
| D03112 | Melanoma in situ of right lower eyelid, including canthus |
| D0312 | Melanoma in situ of left eyelid, including canthus |
| D03121 | Melanoma in situ of left upper eyelid, including canthus |
| D03122 | Melanoma in situ of left lower eyelid, including canthus |
| D0320 | Melanoma in situ of unspecified ear and external auricular canal |
| D0321 | Melanoma in situ of right ear and external auricular canal |
| D0322 | Melanoma in situ of left ear and external auricular canal |
| D0330 | Melanoma in situ of unspecified part of face |
| D0339 | Melanoma in situ of other parts of face |
| D034 | Melanoma in situ of scalp and neck |
| D0351 | Melanoma in situ of anal skin |
| D0352 | Melanoma in situ of breast (skin) (soft tissue) |
| D0359 | Melanoma in situ of other part of trunk |
| D0360 | Melanoma in situ of unspecified upper limb, including shoulder |
| D0361 | Melanoma in situ of right upper limb, including shoulder |
| D0362 | Melanoma in situ of left upper limb, including shoulder |
| D0370 | Melanoma in situ of unspecified lower limb, including hip |
| D0371 | Melanoma in situ of right lower limb, including hip |
| D0372 | Melanoma in situ of left lower limb, including hip |
| D038 | Melanoma in situ of other sites |
| D039 | Melanoma in situ, unspecified |
| D040 | Carcinoma in situ of skin of lip |
| D0410 | Carcinoma in situ of skin of unspecified eyelid, including canthus |
| D0411 | Carcinoma in situ of skin of right eyelid, including canthus |
| D04111 | Carcinoma in situ of skin of right upper eyelid, including canthus |
| D04112 | Carcinoma in situ of skin of right lower eyelid, including canthus |
| D0412 | Carcinoma in situ of skin of left eyelid, including canthus |
| D04121 | Carcinoma in situ of skin of left upper eyelid, including canthus |
| D04122 | Carcinoma in situ of skin of left lower eyelid, including canthus |
| D0420 | Carcinoma in situ of skin of unspecified ear and external auricular canal |
| D0421 | Carcinoma in situ of skin of right ear and external auricular canal |
| D0422 | Carcinoma in situ of skin of left ear and external auricular canal |
| D0430 | Carcinoma in situ of skin of unspecified part of face |
| D0439 | Carcinoma in situ of skin of other parts of face |
| D044 | Carcinoma in situ of skin of scalp and neck |
| D045 | Carcinoma in situ of skin of trunk |
| D0460 | Carcinoma in situ of skin of unspecified upper limb, including shoulder |
| D0461 | Carcinoma in situ of skin of right upper limb, including shoulder |
| D0462 | Carcinoma in situ of skin of left upper limb, including shoulder |
| D0470 | Carcinoma in situ of skin of unspecified lower limb, including hip |
| D0471 | Carcinoma in situ of skin of right lower limb, including hip |
| D0472 | Carcinoma in situ of skin of left lower limb, including hip |
| D048 | Carcinoma in situ of skin of other sites |
| D049 | Carcinoma in situ of skin, unspecified |
| D0500 | Lobular carcinoma in situ of unspecified breast |
| D0501 | Lobular carcinoma in situ of right breast |
| D0502 | Lobular carcinoma in situ of left breast |
| D0510 | Intraductal carcinoma in situ of unspecified breast |
| D0511 | Intraductal carcinoma in situ of right breast |
| D0512 | Intraductal carcinoma in situ of left breast |
| D0580 | Other specified type of carcinoma in situ of unspecified breast |
| D0581 | Other specified type of carcinoma in situ of right breast |
| D0582 | Other specified type of carcinoma in situ of left breast |
| D0590 | Unspecified type of carcinoma in situ of unspecified breast |
| D0591 | Unspecified type of carcinoma in situ of right breast |
| D0592 | Unspecified type of carcinoma in situ of left breast |
| D060 | Carcinoma in situ of endocervix |
| D061 | Carcinoma in situ of exocervix |
| D067 | Carcinoma in situ of other parts of cervix |
| D069 | Carcinoma in situ of cervix, unspecified |
| D070 | Carcinoma in situ of endometrium |
| D071 | Carcinoma in situ of vulva |
| D072 | Carcinoma in situ of vagina |
| D0730 | Carcinoma in situ of unspecified female genital organs |
| D0739 | Carcinoma in situ of other female genital organs |
| D074 | Carcinoma in situ of penis |
| D075 | Carcinoma in situ of prostate |
| D0760 | Carcinoma in situ of unspecified male genital organs |
| D0761 | Carcinoma in situ of scrotum |
| D0769 | Carcinoma in situ of other male genital organs |
| D090 | Carcinoma in situ of bladder |
| D0910 | Carcinoma in situ of unspecified urinary organ |
| D0919 | Carcinoma in situ of other urinary organs |
| D0920 | Carcinoma in situ of unspecified eye |
| D0921 | Carcinoma in situ of right eye |
| D0922 | Carcinoma in situ of left eye |
| D093 | Carcinoma in situ of thyroid and other endocrine glands |
| D098 | Carcinoma in situ of other specified sites |
| D099 | Carcinoma in situ, unspecified |
ICD-10-CM=International Classification of Diseases, 10th Edition Clinical Modification
We studied the comorbidities that affect the risk of inpatient mortality and readmissions by utilizing Elixhauser comorbidity mortality index that has been validated to predict inpatient mortality. It is a continuous variable that ranges from 59 to 171 (the higher the score, the higher association with inpatient mortality).[13] In addition, we considered the effect of presence of acute respiratory failure and demographics (age and gender). Ethnicity is not available in the NRD database. We calculated readmission rate, mortality rate for patients who had a primary diagnosis of COPD with cachexia (COPD-C) and for patients with a primary diagnosis of COPD with no concurrent documentation of cachexia (COPD-NC). Survey procedures in SAS were used to adjust for complex survey design of NRD to produce nationwide estimates for analysis. Categorical and continuous variables were reported as percentage and mean ± standard deviation, respectively. Differences in mean and percentage were assessed using the least square means and Chi-square tests, respectively. Logistic regression was used to analyze the independent impact of cachexia on inpatient mortality (binary outcome). The outcome was adjusted for age, gender, presence of acute respiratory failure, and Elixhauser mortality index, which has been validated in the NRD database.[14] Statistical significance was considered as a two-sided P = 0.05 for all analyses. All analyses were performed using Statistical Analysis Software (SAS) version 9.4 (SAS 9.4, SAS Institute Inc., Cary, NC, USA).
Results
The study cohort consisted of 1,446,431 discharges with a primary diagnosis of COPD identified between January and November 2016–2019. Of these, almost 8% (115,276 cases) had a concurrent diagnosis of cachexia (COPD-C) [Figure 1].
Tables 1 and 2 provide the baseline demographic and clinical characteristics of the study population categorized into COPD-C and COPD-NC. When comparing both groups, in contrast to COPD-NC patients, COPD-C patients were slightly older (mean age of 69.3 vs. 66.6 years, P < 0.0001). Fifty-eight percent of the patient population were female. Patients with pulmonary cachexia were associated with a higher prevalence of alcohol use, drug use, cerebrovascular disease, dementia, and depression. In contrast, COPD-NC patients had a higher prevalence of diabetes mellitus, hypertension, thyroid disorders, and obesity.
Table 1.
Baseline characteristics
| Baseline characteristics | COPD with cachexia, n (%) | COPD without cachexia, n (%) | P |
|---|---|---|---|
| n | 115,276 (8) | 1,331,155 (92) | N/A |
| Age (years), mean±SD | 69.3 (15.0) | 66.6 (16.2) | <0.0001 |
| Female | 67,093 (58.2) | 781,555 (58.7) | 0.0472 |
| Comorbidities | |||
| Alcohol use | 9472 (8.2) | 72,098 (5.4) | <0.0001 |
| Drug abuse | 6576 (5.7) | 62,469 (4.7) | <0.0001 |
| CBVD | 1795 (1.6) | 18,327 (1.4) | 0.0007 |
| Dementia | 7777 (6.7) | 54,637 (4.1) | <0.0001 |
| Paralysis | 1305 (1.1) | 14,229 (1.1) | 0.1679 |
| Depression | 21,787 (18.9) | 235,729 (17.7) | <0.0001 |
| DM | 14,051 (12.2) | 364,736 (27.4) | <0.0001 |
| HTN | 64,910 (56.3) | 896,146 (67.3) | <0.0001 |
| Thyroid disorder | 15,750 (13.7) | 195,568 (14.7) | <0.0001 |
| Valvular disease | 811 (0.7) | 12,220 (0.9) | <0.0001 |
| PVD | 10,746 (9.3) | 83,004 (6.2) | <0.0001 |
| Obesity | 3592 (3.1) | 233,222 (17.5) | <0.0001 |
| Autoimmune disease | 4321 (3.7) | 51,308 (3.9) | 0.2708 |
| Elixhauser mortality index | −1.5 (6.8) | −2.6 (7.4) | <0.0001 |
| Elixhauser readmission index | 2.8 (4.0) | 2.7 (4.1) | <0.0001 |
SD=Standard deviation, CBVD=Cerebrovascular disease, DM=Diabetes mellitus, HTN=Hypertension, PVD=Peripheral vascular disease, COPD=Chronic obstructive lung disease, N/A=Not available
Table 2.
Baseline characteristics
| Baseline characteristics | COPD with cachexia | COPD without cachexia | P |
|---|---|---|---|
| Payor | |||
| Medicare | 84,647 (73.4) | 880,204 (66.1) | <0.0001 |
| Medicaid | 14,532 (12.6) | 201,810 (15.2) | |
| Private | 10,358 (9.0) | 164,105 (12.3) | |
| Self-pay | 2663 (2.3) | 44,930 (3.4) | |
| No charge | 455 (0.4) | 6908 (0.5) | |
| Other | 2506 (2.2) | 31,313 (2.4) | |
| Hospital area | |||
| Central large metropolitan counties | 25,621 (22.2) | 276,512 (20.8) | <0.0001 |
| Fringe large metropolitan counties | 26,664 (23.1) | 322,172 (24.2) | |
| Medium metropolitan counties | 26,748 (23.2) | 287,890 (21.6) | |
| Small metropolitan counties | 12,204 (10.6) | 137,822 (10.4) | |
| Micropolitan counties | 13,699 (11.9) | 159,787 (12.0) | |
| Not micropolitan counties | 9661 (8.4) | 140,510 (10.6) | |
| Socioeconomic status | |||
| 0–25th percentile | 42,173 (36.6) | 506,450 (38.0) | <0.0001 |
| 26th–50th percentile (median) | 32,653 (28.3) | 383,960 (28.8) | |
| 51st–75th percentile | 24,205 (21.0) | 267,683 (20.1) | |
| 76th–100th percentile | 14,754 (12.8) | 155,285 (11.7) |
COPD=Chronic obstructive lung disease
The primary payor for the study population was Medicare, followed by Medicaid. The majority of patients with a primary diagnosis of COPD were admitted to hospitals located in large or medium metropolitan counties. The majority consisted of individuals of low socio-economic status.
Table 3 shows the outcome during index admission, and first subsequent 30-day readmission in the same year, in the same state. Compared to patients with COPD-NC, COPD-C patients had higher inpatient mortality (2.2% vs. 0.5%, P < 0.0001). Furthermore, they had a higher incidence of acute respiratory failure, intubation, ventricular tachycardia (VT), and sudden cardiac arrest (P < 0.001). Subsequently, they had a longer LOS (mean of 5.2 vs. 3.8 days, P < 0.0001) and higher total charges for the hospitalization (mean of $43,723 vs. $31,110 U.S Dollars, P < 0.0001).
Table 3.
Outcomes
| Outcome | COPD with cachexia, n (%) | COPD without cachexia, n (%) | P |
|---|---|---|---|
| During index admission | |||
| Mortality during index admission | 2538 (2.2) | 7026 (0.5) | <0.0001 |
| Mean index LOS, mean±SD | 5.2±8.2 | 3.8±4.8 | <0.0001 |
| Total charges, mean±SD | 43,723.7±125,599.2 | 31,110.9±53,133.6 | |
| Acute respiratory failure | 45,641 (39.6) | 382,841 (28.8) | <0.0001 |
| Intubation | 14,204 (12.3) | 107,863 (8.1) | <0.0001 |
| VT | 795 (0.7) | 7397 (0.6) | <0.0001 |
| SCA | 418 (0.4) | 2084 (0.2) | <0.0001 |
| Cardiogenic shock | 7 (0.0) | 19 (0.0) | 0.0036 |
| Disposition of patient | |||
| Discharged to self-care | 61,002 (52.9) | 955,445 (71.8) | |
| SNF, ICF or other facility | 21,209 (18.4) | 115,309 (8.7) | |
| Discharged with HHC | 27,883 (24.2) | 215,912 (16.2) | |
| During 30-day readmission | |||
| Mortality during first readmission | 1300 (1.1) | 5901 (0.4) | <0.0001 |
| Days to readmission, mean±SD | 13.4±11.9 | 13.6±11.8 | <0.0001 |
| Mean readmission LOS, mean±SD | 6.0±9.5 | 5.4±7.8 | 0.0194 |
| Total readmissions | 23,234 (20.2) | 220,597 (16.6) | <0.0001 |
| 0 | 92,042 (79.8) | 1,110,558 (83.4) | <0.0001 |
| 1 | 19,687 (17.1) | 186,389 (14.0) | |
| 2 | 3016 (2.6) | 29,139 (2.2) | |
| 3 | 452 (0.4) | 4211 (0.3) |
SD=Standard deviation, VT=Ventricular tachycardia, SCA=Sudden cardiac arrest, SNF=Skilled nursing facility, ICF=Intermediate care facility, HHC=Home health care, LOS=Length of stay, COPD=Chronic obstructive lung disease
When examining discharges from the hospital, the majority of patients with COPD-NC were discharged to home/self-care, while patients with COPD-C had higher rates of discharge to a facility or with home health services (42.6% vs. 24.9%).
Compared to patients with COPD-NC, patients with COPD-C had higher inpatient mortality during first readmission within the 30-day index discharge (1.1% vs. 0.4%, P < 0.0001).
Figure 2 displays variables associated with inpatient mortality. Acute respiratory failure is the most important predictor of inpatient mortality for patients admitted primarily with COPD after applying the exclusions mentioned above (OR 7.2, CI 95% 6.7–7.8). Patients with cachexia had 3 times higher odds of inpatient mortality in comparison to patient with no cachexia (OR 3, CI 95% 2.8–3.2). Elderly male patients with a higher Elixhauser mortality index have higher odds of inpatient mortality in comparison to younger female patients with a lower mortality index.
Figure 2.
Odds of inpatient mortality during index hospitalization. The reference age group is 18–60-year-old. ARF: Acute respiratory failure, CI: Confidence interval. The figure was done using JMP® Pro 15.1.0
Discussion
In our study, we intended to increase the accuracy of identifying pulmonary cachexia cases by increasing diagnosis specificity (excluding patients who have other comorbidities associated with cachexia) and limiting case definition to patients with a primary diagnosis of COPD. We also tried to obtain as many cases as possible by increasing the sensitivity of the diagnosis of cachexia.
Multiple etiologies are associated with cachexia. The most common ones are cancer-related cachexia, pulmonary cachexia, human immunodeficiency virus-related cachexia, end-stage renal disease-associated cachexia, and heart failure-associated cachexia (cardiac cachexia).[5]
Cachexia is usually associated with anorexia (decreased caloric intake) and is typically called anorexia-cachexia syndrome, which is described more in patients with malignancies.[15] Increasing caloric intake in anorexia-cachexia syndrome can improve nutrition by overcoming anorexia rather than cachexia pathophysiology. The pathogenesis of cachexia is related to an inflammatory process that is driven by cytokines that promote catabolism[16,17] and increase resting metabolic rate.[4]
In COPD, destruction of normal anatomy due to local increase of inflammatory processes in the lungs leads to altered pulmonary mechanics and subsequent decrease efficiency (increase activity-related energy expenditure). In addition, the latter may be enhanced by increased anaerobic metabolism noticed in COPD.[4] Wilson et al. noted that the body weight was directly related to forced expiratory volume (FEV) in the 1st s (FEV1) and that body weight is independent from FEV1 as a predictor of mortality.[7]
The main finding of our study is that admitted patients with a primary diagnosis of COPD and concurrent weight loss (pulmonary cachexia) have a significantly higher inpatient mortality during index admission and subsequent readmission.
COPD is the fourth principal diagnoses associated with 30-day readmission in the United States with significant health and economic burden.[18] A limited number of studies have assessed the prognostic significance of weight loss and COPD in-hospital mortality. We found that cachexia was a strong predictor of inpatient mortality and prolonged hospitalization. To the best of our knowledge, ours is the only study that reports a strong correlation of cachexia with in-hospital mortality in patients admitted with a primary diagnosis of COPD.
A higher percentage of patients admitted with COPD and cachexia were discharged to a facility or with home health services in comparison with patients without pulmonary cachexia suggesting further increases in the course of care even after discharge.
Our study has some limitations. First, the design of the study is retrospective. Retrospective data collected from an administrative database have a risk of bias related to hospital documentation. Second, the case definition is not 100% specific. The identification of comorbidities is primarily related to their documentation rather than their actual presence, i.e., a comorbidity is defined as absent unless it is documented present. Further, prospective studies are recommended to validate the findings of this study. No anthropometric measurements, laboratory results, imaging reports, or pulmonary function tests are contained in NRD.
Conclusion
Pulmonary cachexia is associated with increased inpatient mortality, prolonged hospital stays, and increased resource utilization. Patients with COPD should have consideration for the evaluation of malnutrition and unintentional weight loss during their hospital stay. As cachexia is a multifactorial condition and the pathophysiological mechanisms are not completely understood, studies designed to develop specific prevention and treatment therapies are needed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Case definition based on Internation Classification for Diseases, Tenth Revision (ICD-10) codes for solid cancers
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Case definition based on Internation Classification for Diseases, Tenth Revision (ICD-10) codes for solid cancers