Approximately 65% of the variability in dyspnea
remained unexplained by the factors examined in our
study. Most individuals in our study showed normal
spirometry results but still carried a substantial
burden of dyspnea, an inconsistency that needs
explanation. Several factors not included in our
analysis may have contributed to the unexplained
variation. Environmental factors (eg, air pollution,
allergen exposure, seasonal variations in symptoms)
are potential contributors to this unexplained
variability. 22 Genetic predispositions could also play a
signiﬁcant role, as suggested by a study that revealed
that parents with dyspnea were 1.8 times more likely
to have offspring with dyspnea.23 Additionally, ﬁtness
could be a contributing factor, especially in
individuals with undiagnosed PRISm, asthma, or
COPD who may restrict their activities to avoid
dyspnea, and hence become deconditioned.6
There were signiﬁcant but modest differences in mean
dyspnea levels across the 17 study sites (data not
shown), which are not explained by the risk factors we
accounted for in our study. Thisﬁnding is not surprising
because some of the potential contributing factors
previously mentioned and other site-speciﬁc factors
(eg, climate, air quality/industrialization, socioeconomic
status) of the catchment population tend to vary across
study sites.
Dyspnea is a complex, subjective symptom that is
modiﬁed by nonrespiratory factors including
psychosocial, social, and environmental inﬂuences.5
Interindividual variability in the perception of dyspnea,
inﬂuenced by these nonrespiratory factors, may play an
important role. A study conducted by Ziegler et al24
assessed the perception of dyspnea in 42 healthy
individuals using a standardized inspiratory resistive
loading stimulus. The study used the modiﬁed Borg
scale to measure dyspnea perception levels. Among the
participants subjected to the same inspiratory resistive
load, 31%, 45%, and 24% of participants classiﬁed their
level of dyspnea as low, intermediate, and high,
respectively. The study revealed that differences between
individuals contribute considerable variability to the
perception of dyspnea, even among healthy participants.
The affective dimension of dyspnea can be captured
using additional questionnaires (eg, Multidimensional
Dyspnea Proﬁle, Dyspnea-12). Studies have explored the
use of the Multidimensional Dyspnea Proﬁle in
TABLE 6] Dyspnea Regressed on Lung Function Variables Representing Severity of Impairment
Disease Group Reversibility of FEV 1, % Post-BD FEV 1/FVC Ratio Post-BD FEV 1 % predicted Overall P Value
Control /C0 0.163 (P ¼ .47) /C0 0.274 (P [ .05) /C0 0.090 (P ¼ .17) .096
Normal spirometry 0.186 ( P ¼ .16) 0.240 (P [ .005) /C0 0.131 (P < .001) < .001
Asthma 0.545 (P [ .01) 0.107 (P ¼ .58) /C0 0.158 (P ¼ .08) .009
COPD 0.392 (P [ .002) /C0 0.307 (P [ .05) /C0 0.075 (P ¼ .37) < .001
PRISm /C0 0.290 (P ¼ .39) 0.854 (P [ .002) /C0 0.650 (P [ .004) < .001
Dyspnea regressed on lung function variables representing severity of impairment, after removing contributions of patient-speciﬁc factors and spirometry
disease group Tables 4 and 5 (1.7% of variability explained). Boldface indicates statitistical signiﬁcance. BD ¼ bronchodilator; PRISm ¼ preserved ratio
impaired spirometry.
TABLE 7] Unadjusted and Adjusted Dyspnea Associations With Quality of Life (SF-36)
Measure
Unadjusted Adjusted
Dyspnea Coefﬁcient (95% CI) P Value Dyspnea Coef ﬁcient (95% CI) P Value
Physical functioning /C0 0.693 (/C0 0.718 to/C0 0.668) < .001 /C0 0.655 (/C0 0.680 to/C0 0.630) < .001
Physical health limitations /C0 0.634 (/C0 0.666 to/C0 0.603) < .001 /C0 0.628 (/C0 0.661 to/C0 0.595) < .001
Emotional problems /C0 0.403 (/C0 0.438 to/C0 0.369) < .001 /C0 0.407 (/C0 0.443 to/C0 0.370) < .001
Energy/fatigue /C0 0.454 (/C0 0.479 to/C0 0.428) < .001 /C0 0.452 (/C0 0.479 to/C0 0.425) < .001
Emotional well-being /C0 0.230 (/C0 0.256 to/C0 0.204) < .001 /C0 0.239 (/C0 0.266 to/C0 0.213) < .001