graph LR
Dyspnea["Dyspnea"]
Protease_Antiprotease_Imbalance_MMP_2_TIMP_2_Axis["Protease-Antiprotease Imbalance (MMP-2/TIMP-2 Axis)"]
Open_top_vascularized_alveolus_on_chip_whole_cigarette_smoke_model["Open-top vascularized alveolus-on-chip whole cigarette smoke model"]
Mucus_Hypersecretion["Mucus Hypersecretion"]
Air_Pollution["Air Pollution"]
Cellular_Senescence["Cellular Senescence"]
Airway_Remodeling["Airway Remodeling"]
Smoking["Smoking"]
Chronic_Inflammation["Chronic Inflammation"]
Oxidative_Stress_and_Mitochondrial_Dysfunction["Oxidative Stress and Mitochondrial Dysfunction"]
Forced_Expiratory_Volume_in_1_Second_FEV1["Forced Expiratory Volume in 1 Second (FEV1)"]
Airflow_Limitation["Airflow Limitation"]
Respiratory_Failure["Respiratory Failure"]
Occupational_Dust_and_Chemicals["Occupational Dust and Chemicals"]
SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation["SIRT1-Mediated NAD+ Signaling and Protective Deacetylation"]
NFE2L2["NFE2L2"]
Hypercapnia["Hypercapnia"]
Hypoxemia["Hypoxemia"]
Cuproptosis_Driven_Cell_Death["Cuproptosis-Driven Cell Death"]
Alveolar_Destruction["Alveolar Destruction"]
Patient_derived_epithelial_endothelial_COPD_airway_on_a_chip["Patient-derived epithelial-endothelial COPD airway-on-a-chip"]
Progressive_Respiratory_Impairment["Progressive Respiratory Impairment"]
Exercise_Intolerance["Exercise Intolerance"]
Airflow_Limitation -.-> Progressive_Respiratory_Impairment
Chronic_Inflammation --> Cuproptosis_Driven_Cell_Death
Oxidative_Stress_and_Mitochondrial_Dysfunction --> Protease_Antiprotease_Imbalance_MMP_2_TIMP_2_Axis
SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation --> Chronic_Inflammation
SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation --> Cellular_Senescence
SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation --> Alveolar_Destruction
SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation --> Oxidative_Stress_and_Mitochondrial_Dysfunction
Protease_Antiprotease_Imbalance_MMP_2_TIMP_2_Axis --> Alveolar_Destruction
Cuproptosis_Driven_Cell_Death --> Chronic_Inflammation
Dyspnea --> Exercise_Intolerance
Respiratory_Failure --> Hypoxemia
Respiratory_Failure --> Hypercapnia
Smoking --> Chronic_Inflammation
Smoking --> Cuproptosis_Driven_Cell_Death
Air_Pollution --> Oxidative_Stress_and_Mitochondrial_Dysfunction
Occupational_Dust_and_Chemicals --> Chronic_Inflammation
Open_top_vascularized_alveolus_on_chip_whole_cigarette_smoke_model --> Alveolar_Destruction
Open_top_vascularized_alveolus_on_chip_whole_cigarette_smoke_model --> Oxidative_Stress_and_Mitochondrial_Dysfunction
Patient_derived_epithelial_endothelial_COPD_airway_on_a_chip --> Mucus_Hypersecretion
Patient_derived_epithelial_endothelial_COPD_airway_on_a_chip --> Airway_Remodeling
Airflow_Limitation -.-> Forced_Expiratory_Volume_in_1_Second_FEV1
NFE2L2 --> SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation
style Dyspnea fill:#fef3c7
style Protease_Antiprotease_Imbalance_MMP_2_TIMP_2_Axis fill:#dbeafe
style Open_top_vascularized_alveolus_on_chip_whole_cigarette_smoke_model fill:#ccfbf1
style Mucus_Hypersecretion fill:#dbeafe
style Air_Pollution fill:#dcfce7
style Cellular_Senescence fill:#dbeafe
style Airway_Remodeling fill:#dbeafe
style Smoking fill:#dcfce7
style Chronic_Inflammation fill:#dbeafe
style Oxidative_Stress_and_Mitochondrial_Dysfunction fill:#dbeafe
style Forced_Expiratory_Volume_in_1_Second_FEV1 fill:#e0e7ff
style Airflow_Limitation fill:#dbeafe
style Respiratory_Failure fill:#fef3c7
style Occupational_Dust_and_Chemicals fill:#dcfce7
style SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation fill:#dbeafe
style NFE2L2 fill:#f3e8ff
style Hypercapnia fill:#fef3c7
style Hypoxemia fill:#fef3c7
style Cuproptosis_Driven_Cell_Death fill:#dbeafe
style Alveolar_Destruction fill:#dbeafe
style Patient_derived_epithelial_endothelial_COPD_airway_on_a_chip fill:#ccfbf1
style Progressive_Respiratory_Impairment fill:#fee2e2,stroke:#dc2626,stroke-dasharray: 5 5
style Exercise_Intolerance fill:#fef3c7
graph LR
Central_Sensitization["Central Sensitization"]
Neuroinflammation["Neuroinflammation"]
Small_Fiber_Pathology["Small Fiber Pathology"]
Neuroinflammation --> Central_Sensitization
Small_Fiber_Pathology --> Central_Sensitization
style Central_Sensitization fill:#dbeafe
style Neuroinflammation fill:#dbeafe
style Small_Fiber_Pathology fill:#dbeafe
name: com_Chronic_Obstructive_Pulmonary_Disease__Fibromyalgia
creation_date: '2026-06-26T00:00:00Z'
curation_status: CANDIDATE
notes: >-
Cross-system comorbidity: fibromyalgia is over-represented in COPD. Surfaced
as a strong positive both-in-dismech ICEES EHR signal (UNC PCD cohort,
chi-square=52.3, p=4.7e-13) and corroborated by a cross-sectional study
reporting higher fibromyalgia prevalence in COPD than controls. Directionality
is UNKNOWN (cross-sectional evidence); the proposed mechanism is central
sensitization driven by chronic pain, systemic inflammation, poor sleep, and
depression in COPD.
disease_a:
slug: Chronic_Obstructive_Pulmonary_Disease
preferred_term: chronic obstructive pulmonary disease
term:
id: MONDO:0005002
label: chronic obstructive pulmonary disease
disease_b:
slug: Fibromyalgia
preferred_term: fibromyalgia
term:
id: MONDO:0005546
label: fibromyalgia
directionality: UNKNOWN
hypotheses:
- description: >-
Hypothesis: chronic pain, systemic inflammation, sleep disturbance, and
depressive symptoms in COPD promote central sensitization, increasing the
likelihood of comorbid fibromyalgia, particularly in women.
evidence:
- reference: PMID:40852783
reference_title: "Prevalence and clinical characteristics of fibromyalgia syndrome in individuals with chronic obstructive pulmonary disease: A cross-sectional study."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The prevalence of fibromyalgia syndrome was significantly greater in individuals with chronic obstructive pulmonary disease (16%) than in healthy controls (3%)"
explanation: >-
Cross-sectional study quantifies the elevated fibromyalgia prevalence in
COPD relative to matched controls.
- reference: PMID:40852783
reference_title: "Prevalence and clinical characteristics of fibromyalgia syndrome in individuals with chronic obstructive pulmonary disease: A cross-sectional study."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "These findings underscore the clinical relevance of fibromyalgia syndrome as a comorbidity in chronic obstructive pulmonary disease, particularly in women"
explanation: >-
Authors frame fibromyalgia as a clinically relevant COPD comorbidity,
with a female predominance.
pathophysiology:
- name: Central sensitization from chronic COPD burden
description: >-
Persistent pain, inflammatory burden, hypoxia-related symptoms, poor sleep,
and mood disturbance in COPD may provoke central sensitization, lowering
pain thresholds and manifesting as fibromyalgia.
biological_processes:
- preferred_term: sensory perception of pain
term:
id: GO:0019233
label: sensory perception of pain
evidence:
- reference: PMID:40852783
reference_title: "Prevalence and clinical characteristics of fibromyalgia syndrome in individuals with chronic obstructive pulmonary disease: A cross-sectional study."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Patients with both chronic obstructive pulmonary disease and fibromyalgia syndrome frequently reported increased fatigue, sleep disturbances, and depressive symptoms."
explanation: >-
Co-affected patients report fatigue, sleep disturbance, and depression,
features consistent with a central-sensitization phenotype.
association_signals:
- source: ICEES
method: EHR_COHORT_ASSOCIATION
signal_disorder_a_id: MONDO:0005002
signal_disorder_b_id: MONDO:0005546
population: >-
ICEES KG 8-20-2024, UNC Health primary-ciliary-dyskinesia (PCD) cohort
(condition-specific base population), patient-level chi-square contingency.
mapping_notes: >-
ICEES reports this pair as a positive correlation. Chi-square is not
multiple-testing corrected and is conditioned on the PCD base population,
so it corroborates rather than establishes the association. The row quoted
is the strongest PCD cohort-year (2020).
directionality: UNKNOWN
statistics:
metrics:
- metric_type: CHI_SQUARE
metric_value: 52.3223044040033
p_value: 4.709944488099253e-13
notes: >-
ICEES PCD 2020 cohort co-occurrence of COPD and fibromyalgia (N=4753);
strong, highly significant positive association.
evidence:
- reference: ICEES:MONDO_0005002__MONDO_0005546
reference_title: "chronic obstructive pulmonary disease / fibromyalgia (ICEES KG)"
supports: SUPPORT
evidence_source: OTHER
snippet: "PCD_UNC_patient_2020_v6_binned_deidentified | 52.3223044040033 | 1 | 4.709944488099253e-13 | 4753"
explanation: >-
ICEES UNC EHR cohort shows a strong, highly significant COPD-fibromyalgia
co-occurrence in the 2020 PCD cohort.