graph LR
Chest_Tightness["Chest Tightness"]
Exercise_Intolerance["Exercise Intolerance"]
Sleep_Disturbance["Sleep Disturbance"]
Type_2_Immune_Response___Th2_Signaling["Type 2 Immune Response / Th2 Signaling"]
IL4["IL4"]
Wheezing["Wheezing"]
IL13["IL13"]
Airway_Inflammation["Airway Inflammation"]
Early_Life_Rhinovirus_Wheezing_Illness_and_Asthma_Inception["Early-Life Rhinovirus Wheezing Illness and Asthma Inception"]
Rapid_Breathing["Rapid Breathing"]
Respiratory_Distress["Respiratory Distress"]
STAT3["STAT3"]
Coughing["Coughing"]
Bronchoconstriction["Bronchoconstriction"]
Reduced_Exercise_Tolerance["Reduced Exercise Tolerance"]
CDHR3["CDHR3"]
Anxiety["Anxiety"]
Airway_Remodeling["Airway Remodeling"]
Mucus_Overproduction["Mucus Overproduction"]
ADAM33["ADAM33"]
House_Dust_Mite_Allergen_Protease_Induced_Epithelial_Oxidant_Signaling["House Dust Mite Allergen Protease-Induced Epithelial Oxidant Signaling"]
Fatigue["Fatigue"]
Cyanosis["Cyanosis"]
SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation["SIRT1-Mediated NAD+ Signaling and Protective Deacetylation"]
Airway_Inflammation --> Bronchoconstriction
Type_2_Immune_Response___Th2_Signaling --> Airway_Inflammation
Type_2_Immune_Response___Th2_Signaling --> Mucus_Overproduction
Bronchoconstriction --> Wheezing
Bronchoconstriction --> Chest_Tightness
Bronchoconstriction --> Rapid_Breathing
Bronchoconstriction --> Respiratory_Distress
Bronchoconstriction --> Cyanosis
Bronchoconstriction --> Exercise_Intolerance
Bronchoconstriction --> Reduced_Exercise_Tolerance
Bronchoconstriction --> Fatigue
Bronchoconstriction --> Anxiety
Mucus_Overproduction --> Coughing
Mucus_Overproduction --> Sleep_Disturbance
SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation --> Type_2_Immune_Response___Th2_Signaling
SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation --> Mucus_Overproduction
SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation --> Airway_Remodeling
SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation --> Bronchoconstriction
Early_Life_Rhinovirus_Wheezing_Illness_and_Asthma_Inception --> Type_2_Immune_Response___Th2_Signaling
House_Dust_Mite_Allergen_Protease_Induced_Epithelial_Oxidant_Signaling --> Airway_Inflammation
Wheezing --> Respiratory_Distress
Wheezing --> Reduced_Exercise_Tolerance
IL4 --> Type_2_Immune_Response___Th2_Signaling
IL13 --> Type_2_Immune_Response___Th2_Signaling
ADAM33 --> Airway_Remodeling
STAT3 --> SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation
CDHR3 --> Early_Life_Rhinovirus_Wheezing_Illness_and_Asthma_Inception
style Chest_Tightness fill:#fef3c7
style Exercise_Intolerance fill:#fef3c7
style Sleep_Disturbance fill:#fef3c7
style Type_2_Immune_Response___Th2_Signaling fill:#dbeafe
style IL4 fill:#f3e8ff
style Wheezing fill:#fef3c7
style IL13 fill:#f3e8ff
style Airway_Inflammation fill:#dbeafe
style Early_Life_Rhinovirus_Wheezing_Illness_and_Asthma_Inception fill:#dbeafe
style Rapid_Breathing fill:#fef3c7
style Respiratory_Distress fill:#fef3c7
style STAT3 fill:#f3e8ff
style Coughing fill:#fef3c7
style Bronchoconstriction fill:#dbeafe
style Reduced_Exercise_Tolerance fill:#fef3c7
style CDHR3 fill:#f3e8ff
style Anxiety fill:#fef3c7
style Airway_Remodeling fill:#dbeafe
style Mucus_Overproduction fill:#dbeafe
style ADAM33 fill:#f3e8ff
style House_Dust_Mite_Allergen_Protease_Induced_Epithelial_Oxidant_Signaling fill:#dbeafe
style Fatigue fill:#fef3c7
style Cyanosis fill:#fef3c7
style SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation fill:#dbeafe
graph LR
Small_Fiber_Pathology["Small Fiber Pathology"]
Neuroinflammation["Neuroinflammation"]
Central_Sensitization["Central Sensitization"]
Neuroinflammation --> Central_Sensitization
Small_Fiber_Pathology --> Central_Sensitization
style Small_Fiber_Pathology fill:#dbeafe
style Neuroinflammation fill:#dbeafe
style Central_Sensitization fill:#dbeafe
name: com_Asthma__Fibromyalgia
creation_date: '2026-06-26T00:00:00Z'
curation_status: CANDIDATE
notes: >-
Bidirectional comorbidity between asthma and fibromyalgia, supported by
population-based and case-control evidence (asthma over-represented in
fibromyalgia, OR~1.9; fibromyalgia over-represented in asthma, ~17% vs ~3%),
and by a strong ICEES EHR signal (UNC PCD cohort, chi-square=81.6, p=1.7e-19).
Directionality is UNKNOWN: both directions are documented and the ICEES
signal is MIXED (positive and negative correlation edges across cohort-years).
Proposed mechanism is central sensitization with shared anxiety/depression and
altered symptom perception.
disease_a:
slug: Asthma
preferred_term: asthma
term:
id: MONDO:0004979
label: asthma
disease_b:
slug: Fibromyalgia
preferred_term: fibromyalgia
term:
id: MONDO:0005546
label: fibromyalgia
directionality: UNKNOWN
hypotheses:
- description: >-
Hypothesis: shared central sensitization, chronic symptom burden, and high
rates of anxiety and depression link asthma and fibromyalgia; fibromyalgia
also alters dyspnea perception, worsening asthma control.
evidence:
- reference: PMID:40011987
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The prevalence of bronchial asthma was higher in patients with FM compared with the controls, with an odds ratio (OR) of 1.91."
explanation: >-
Population-based case-control study quantifies elevated asthma prevalence
among fibromyalgia patients.
- reference: PMID:41017472
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The prevalence of fibromyalgia in the asthma group was 16.7% compared to 3.3% in controls"
explanation: >-
Case-control study shows the reciprocal elevation of fibromyalgia among
asthma patients, supporting a bidirectional association.
pathophysiology:
- name: Central sensitization and altered symptom perception
description: >-
Central sensitization shared between asthma and fibromyalgia, together with
comorbid anxiety/depression, may amplify symptom perception (including
dyspnea), reinforcing the clinical overlap and worsening asthma control.
biological_processes:
- preferred_term: sensory perception of pain
term:
id: GO:0019233
label: sensory perception of pain
association_signals:
- source: ICEES
method: EHR_COHORT_ASSOCIATION
signal_disorder_a_id: MONDO:0004979
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 MIXED correlation (both positively_ and
negatively_correlated_with edges across cohort-years/binning); the row
quoted is the strongest PCD cohort-year (2020). Chi-square is not
multiple-testing corrected and is conditioned on the PCD base population,
so it corroborates rather than establishes the association.
directionality: UNKNOWN
statistics:
metrics:
- metric_type: CHI_SQUARE
metric_value: 81.55545973820404
p_value: 1.7041172557520145e-19
notes: >-
ICEES PCD 2020 cohort co-occurrence of asthma and fibromyalgia
(N=4753); strong association, direction reported inconsistently.
evidence:
- reference: ICEES:MONDO_0004979__MONDO_0005546
supports: SUPPORT
evidence_source: OTHER
snippet: "PCD_UNC_patient_2020_v6_binned_deidentified | 81.55545973820404 | 1 | 1.7041172557520145e-19 | 4753"
explanation: >-
ICEES UNC EHR cohort shows a strong asthma-fibromyalgia co-occurrence in
the 2020 PCD cohort.
- source: LITERATURE
method: LITERATURE_ASSOCIATION
population: >-
Leumit Health Services (Israel) population-based case-control cohort
(~750,000 members); odds of bronchial asthma in fibromyalgia vs controls.
directionality: UNKNOWN
statistics:
metrics:
- metric_type: OR
metric_value: 1.91
notes: Odds ratio of bronchial asthma among fibromyalgia patients vs matched controls.
evidence:
- reference: PMID:40011987
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The prevalence of bronchial asthma was higher in patients with FM compared with the controls, with an odds ratio (OR) of 1.91."
explanation: >-
Population-based odds ratio for asthma among fibromyalgia patients.