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1.  Small Airway Impairment and Bronchial Hyperresponsiveness in Asthma Onset 
Our study tried to find a relationship between baseline FEF25-75% and airway hyperresponsiveness (AHR) and whether a greater FEF25-75% impairment may be a marker of a more severe hyperresponsiveness in subjects with normal FEV1 and FEV1/FVC and suggestive asthma symptoms. Besides, we tried to asses a FEF25-75% cut-off value to identify hyper-reactive subjects.
4,172 subjects (2,042 M; mean age: 38.3±14.9; mean FEV1 % predicted: 100.5±12.7 and FEV1/FVC: 85.4±6.8) were examined after performing a methacholine (Mch) test. All subjects reported a symptom onset within 3 years before the test. Subjects with PD20<400 or >400 µg were arbitrarily considered affected by moderate/severe and borderline AHR, respectively.
PD20 values were 213 (IQR:86-557), 340 (IQR:157-872) and 433 (IQR:196-1032) µg in subjects with baseline FEF25-75≤50%, FEF25-75 between 50 and 70% and FEF25-75>70% respectively (P<0.0001). Only in moderate/severe hyper-reactive subjects (excluded borderlines), PD20 was lower in the FEF25-75≤50% subgroup than in the 1 with FEF25-75>70%. The hyperreactive subjects percentage, was higher in those with FEF25-75≤50% and lower in those with FEF25-75>70% (P<0.0001). FEF25-75<50% (compared to FEF25-75>70%) was a higher AHR risk factor, especially in subjects with moderate/severe AHR (OR: 2.18 [IQR:1.41-3.37]; P<0.0001). Thresholds yielding the highest combined sensitivity/specificity for FEF25-75% were 75.19 (area under curve [AUC]: 0.653) and 74.95 (AUC:0.688) in subjects with PD20<2,400 and <400 µg respectively. FEV1, FVC, and FEV1/FVC measured in subjects with different FEF25-75≤50%, FEF25-75>50 and ≤70% or FEF25-75>70% levels were similar both in normoreactive and hyperreactive subjects.
At asthma onset, reduced baseline FEF25-75 values with normal FEV1 and FEV1/FVC may predict AHR. Detectable predictive cut-off values do not exist because even normoreactive subjects can show lower FEF25-75 values. Furthermore, a greater FEF25-75 reduction may be associated to a more severe AHR, suggesting a possible FEF25-75 role in the management of asthma when FEV1 and FEV1/FVC are normal.
PMCID: PMC4021243  PMID: 24843800
Airway hyperresponsiveness; small airways; methacholine test; asthma; FEF25-75; diagnosis
2.  Obesity can influence children’s and adolescents’ airway hyperresponsiveness differently 
Literature is still arguing about a possible relationship between airway hyperresponsiveness (AHR) and body mass index (BMI). This study aimed at evaluating the influence of BMI on AHR and pulmonary function in children and adolescents that performed a methacholine test for suggestive asthma symptoms.
799 consecutive children/adolescents (535 M; mean age: 15 ± 3 yrs; median FEV1% predicted: 101.94% [93.46-111.95] and FEV1/FVC predicted: 91.07 [86.17-95.38]), were considered and divided into underweight, normal, overweight and obese. Different AHR levels were considered as moderate/severe (PD20 ≤ 400 μg) and borderline (PD20 > 400 μg).
536 children/adolescents resulted hyperreactive with a median PD20 of 366 μg [IQR:168–1010.5]; 317 patients were affected by moderate/severe AHR, whereas 219 showed borderline hyperresponsiveness. Obese subjects aged > 13 years showed a lower (p = 0.026) median PD20 (187μg [IQR:110–519]) compared to overweight (377 μg [IQR:204–774]) and normal-weight individuals’ values (370.5 μg [IQR:189–877]). On the contrary, median PD20 observed in obese children aged ≤ 13 years (761 μg [IQR:731–1212]) was higher (p = 0.052) compared to normal-weight children’s PD20 (193 μg [IQR:81–542]) and to obese adolescents’ values (aged > 13 years) (p = 0.019). Obesity was a significant AHR risk factor (OR:2.853[1.037-7.855]; p = 0.042) in moderate/severe AHR adolescents. Females showed a higher AHR risk (OR:1.696[1.046-2.751] p = 0.032) compared to males. A significant relationship was found between BMI and functional parameters (FEV1, FVC, FEV1/FVC) only in hyperreactive females.
Obesity seems to influence AHR negatively in female but not in male adolescents and children. In fact, AHR is higher in obese teenagers, in particular in those with moderate/severe hyperresponsiveness, and may be mediated by obesity-associated changes in baseline lung function.
PMCID: PMC3844670  PMID: 24028436
Airway hyperresponsiveness; Asthma; Body mass index; Children and adolescents; Methacholine test; Obesity
3.  BMI can influence adult males’ and females’ airway hyperresponsiveness differently 
Epidemiological data indicate that obesity is a risk factor for asthma, but scientific literature is still debating the association between changes in body mass index (BMI) and airway hyperresponsiveness (AHR).
This study aimed at evaluating the influence of BMI on AHR, in outpatients with symptoms suggestive of asthma.
4,217 consecutive adult subjects (2,439 M; mean age: 38.2±14.9 yrs; median FEV1 % predicted: 100 [IQR:91.88-107.97] and FEV1/FVC % predicted: 85.77% [IQR:81.1-90.05]), performed a methacholine challenge test for suspected asthma. Subjects with PD20 < 200 or 200 < PD20 < 800 or PD20 > 800 were considered affected by severe, moderate or mild AHR, respectively.
A total of 2,520 subjects (60% of all cases) had a PD20 < 3,200 μg, with a median PD20 of 366 μg [IQR:168–1010.5]; 759, 997 and 764 patients were affected by mild, moderate and severe AHR, respectively. BMI was not associated with increasing AHR in males. On the contrary, obese females were at risk for AHR only when those with moderate AHR were considered (OR: 1.772 [1.250-2.512], p = 0.001). A significant reduction of FEV1/FVC for unit of BMI increase was found in moderate AHR, both in males (β = −0.255; p =0.023) and in females (β = −0.451; p =0.017).
Our findings indicate that obesity influences AHR only in females with a moderate AHR level. This influence may be mediated by obesity-associated changes in baseline lung function.
PMCID: PMC3529699  PMID: 23157852
Airway hyperresponsiveness; asthma; body mass index; males and females; methacholine test; obesity
4.  Seasons can influence the results of the methacholine challenge test 
Annals of Thoracic Medicine  2012;7(2):61-68.
This study tried to evaluate whether a methacholine test may be influenced by the seasons.
We considered 4826 consecutive subjects with normal spirometry (50.53% males; age: 35.1±16.2; forced expiratory volume in one second: 99.5±13.0%) who underwent a methacholine test for suspected asthma symptoms between 2000 and 2010. They were subdivided into four groups, like the seasons, according to the test dates.
A total of 1981 (41%) resulted normal (no PD20 was obtained with 2400 μg of methacholine); the others showed a mean LogPD20 of 2.52±0.5 μg. The number of subjects with bronchial hyper-responsiveness (BHR) found in autumn (789, 62.3%) was higher than in summer (583, 56.7%; P=0.03). A higher number of females and overweight/obese subjects showed a BHR in autumn compared with the other seasons. The spring mean LogPD20 value (2.48±0.48 μg) was lower if compared with the one measured in summer (2.59±0.49 μg; P=0.05). LogPD20 value was lower in females and non-smokers in spring compared with summer (P<0.05). Overweight/obese non-smokers showed a lower LogPD20 in spring and autumn compared with that in summer (P<0.05). Autumn was a risk factor (OR: 1.378; P=0.001) for BHR (using a PD20 <2 400 μg as BHR limit), while spring (OR: 1.330; P=0.021) and autumn (OR: 1.331; P=0.020) were risk factors for a more severe BHR (using a PD20 <400 μg as BHR limit).
There was a higher probability of finding BHR in outpatients with suspected asthma in autumn and spring compared with summer. Spring is the season where BHR may be more severe. Females and overweight/obese subjects were those mainly involved in this seasonal variability of BHR.
PMCID: PMC3339205  PMID: 22558009
Airway; asthma; bronchial hyper-responsiveness; methacholine challenge test; season

Results 1-4 (4)