influence of outdoor temperature and humidity on the methacholine challenge test

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  • ORIGINAL PAPER

    Influence of outdoor temperature and humidityon the methacholine challenge test

    Bruno Sposato Marco Scalese

    Andrea Pammolli Carlo Pareo Raffaele Scala

    Received: 21 February 2012 / Accepted: 18 July 2012 / Published online: 1 August 2012

    Springer Science+Business Media B.V. 2012

    Abstract Objective of this study was to evaluate

    whether outdoor temperature and humidity can influ-

    ence methacholine test results in outpatients living in

    temperate areas. 4,723 subjects (2,391 males; age:

    35.1 16.15; FEV1 = 100.36 % [relative interquar-

    tile range (IQR):92.34108.8]) that performed metha-

    choline tests for suspected asthma between 2000 and

    2010 were considered. Outdoor minimum, mean, and

    maximum temperature values (C), relative humidity(%), and dew point (Tdp), registered when performing

    the tests, were examined. Airways hyperresponsive

    patients, with PD20 (provocative dose to obtain a 20 %

    fall in FEV1) \3,200 lg were 2,889 (61.2 %) andmedian PD20 was 359 lg [IQR:160-967]. On receivingoperating curve (ROC) analysis, temperature, humidity,

    and Tdp did not significantly predict airways hyperre-

    sponsiveness (AHR), even using a 200, 800, and

    3,200 lg cutoffs to identify AHR. When subjects weresubdivided into subgroups, according to different levels

    of temperature, humidity, and dew point, no differences

    in PD20 and prevalence were found. Only a higher

    number of hyperresponsive subjects was detected in

    smokers when they were tested in hot and humid

    conditions. A weak but significantly positive relation-

    ship between PD20 and mean, maximum, and minimum

    temperatures was detected in severe hyperresponsive

    subjects (PD20 \ 200 lg) (r = 0.100, 0.112, 0.110,respectively; p = 0.001). The regression logistic model

    showed that maximum temperature was a significantly

    protective factor for AHR (OR:0.995, 95 % CI:

    0.9820.998; p = 0.012) especially in severe hyperre-

    sponsive subjects (OR:0.988, 95 % CI: 0.9770.999;

    p = 0.035). In conclusion, weather conditions do not

    seem to influence PD20 values obtained with metha-

    choline tests in real life. Hot and humid environments

    may increase the prevalence of AHR in smokers while a

    temperature increase may reduce the AHR risk espe-

    cially in severe hyperresponsive subjects.

    This article was presented at Amsterdam 2011 Congress of

    European Respiratory Society as Poster presentation (number

    P4049) in Thematic Poster Session on 09/27/2011 and

    published only as an Abstract in Abstract book: Eur Respir J

    2011; 38: Suppl. 55, 739 s. However, this manuscript has never

    been submitted in this form for publication elsewhere. The

    authors alone are responsible for the contents and writing of the

    paper.

    B. Sposato (&)Unit of Pneumology, Misericordia Hospital,

    Via Senese 161, 58100 Grosseto, Italy

    e-mail: bsposat@tin.it

    M. Scalese

    Institute of Clinical Physiology, National Research

    Council (CNR), Pisa, Italy

    A. Pammolli

    Department of Physiopathology, Experimental Medicine

    and Public Health University of Siena, Siena, Italy

    C. Pareo

    Unit of Pneumology, Carlo Urbani Hospital, Jesi, Italy

    R. Scala

    Unit of Pneumology and UTIP, S.Donato Hospital,

    Arezzo, Italy

    123

    Aerobiologia (2013) 29:187200

    DOI 10.1007/s10453-012-9272-0

  • Keywords Airway hyperresponsiveness Temperature Humidity Methacholine test Asthma Environment

    1 Introduction

    Asthma is a chronic inflammatory disease of the

    airways characterized by bronchial obstruction, often

    reversible either spontaneously or with treatment. It is

    also characterized by airways hyperresponsiveness

    (AHR) that can be defined as an exaggerated airways

    obstructive response to a variety of pharmacological,

    chemical, and physical stimuli (histamine, methacho-

    line, cold air, etc.) (ATS 2000). In subjects with

    suspected symptoms of asthma and a normal baseline

    spirometry without a significant increase in lung

    function after inhaling bronchodilators, it is often

    necessary to perform a methacholine challenge test to

    detect AHR and therefore to confirm a diagnosis of

    asthma. In case the provocative dose or concentration

    (PD20 or PC20) of methacholine required to obtain a

    20 % fall in forced expiratory volume in one second

    (FEV1) is lower after the test, the possibility that the

    suggestive symptoms may be due to asthma is high,

    whereas this probability is low if PD20 or PC20 values

    are higher (ATS 2000). AHR seems to be character-

    ized by seasonal variations according to the changes in

    seasonal exposition to various allergens (pollens and

    house dust mites) (Tilles and Bardana 1997). In fact, a

    higher exposure to house dust mites in autumn, when

    they increase in number, or to a greater quantity of

    pollens in spring, seems to increase AHR in subjects

    with rhinitis or asthma (Riccioni et al. 2001; van der

    Heide et al. 1997; Beier et al. 2003). Also, respiratory

    infections, especially in cold seasons, might increase

    hyperresponsiveness in asthmatics (Busse 1990), thus

    influencing AHR variability.

    On the contrary, it is not clear whether temperature

    and humidity may have a direct influence on AHR.

    Extreme values of temperature and humidity and a

    prolonged exposure to them may determine AHR

    variations (Helenius et al. 1996; Langdeau et al. 2000;

    Bougalt et al. 2010). In fact, some studies highlighted

    how AHR prevalence, induced by methacholine, was

    higher in athletes that inhaled cold and humid air during

    training in comparison with those that performed

    training in environments with either dry air or a mixture

    of dry and humid air (Hemingson et al. 2004; Langdeau

    et al. 2000; Bougalt et al. 2010). Furthermore, very high

    and very low values of humidity (95 %) and temper-

    ature (-18 C), respectively, can increase exercise-induced bronchoconstriction (Stensrud et al. 2006,

    2007). However, these conclusions were drawn after

    studying athletes and not common people; furthermore,

    these subjects were often studied only in extreme

    environmental conditions, and sometimes, results were

    obtained in artificial indoor environments and only with

    exercise challenge testing. On the other hand, a non-

    extreme temperature and humidity seem to influence

    weakly exercise-induced AHR (Koh and Choi 2002)

    but not methacholine- or histamine-induced AHR (Koh

    and Choi 2002; Schmidt and Bundgaard 1986; Tessier

    et al. 1988) in subjects with asthma who are not athletes.

    However, these studies were carried out on few patients

    and therefore there are still doubts whether exposure to

    normal range of outdoor temperature and humidity,

    which alternate during the seasons, may influence

    AHR. Especially, we do not know if a methacholine

    challenge test results may be differently influenced by a

    higher or lower value of environmental outdoor tem-

    perature and/or humidity to which a subject is exposed

    before the test. Therefore, the aim of this study was to

    evaluate whether the results of a methacholine chal-

    lenge test can be influenced by different daily outdoor

    temperature and humidity values when the test is

    performed on a large number of outpatients living in

    temperate climates where temperature and humidity

    never reach extreme values.

    2 Materials and methods

    2.1 Study design and subjects

    For this retrospective study, we took out from the

    spirometer data files of our pneumology departments

    of Grosseto and Arezzo (Tuscany, Italy) and analyzed

    the results of 5,023 consecutive methacholine chal-

    lenge tests performed between 2000 and 2010. All

    tests were carried out to confirm or exclude an asthma

    diagnosis. In fact, all patients had suspected asthma

    symptoms (unexplained episodes of cough and/or

    wheezing and/or dyspnea) with a normal spirometry

    and therefore, for this reason, they were subjected to a

    methacholine challenge test. For every test, FEV1,

    FEV1/FVC, forced vital capacity (FVC), PD20FEV1,

    smoking habits, and body mass index (BMI) were

    188 Aerobiologia (2013) 29:187200

    123

  • considered. Also, minimum, medium, and maximum

    values of temperature (T), relative humidity (H), and

    temperature dew point (Tdp), measured on the days

    when the tests were performed, were also taken into

    account. The purpose was to relate T, H, and Tdp with

    the results of the methacholine tests measured on the

    same date.

    Only 4,723 consecutive subjects (2,391 M; mean

    age 35.1 16.17; median FEV1 % 100.36 [IQR:92.24

    108.75] and FEV1/FVC 86.33 [IQR:81.590.88])

    were suitable for the study. Three hundred subjects

    were excluded. Most of them had not completed the

    challenge: some were intolerant to testing and others

    had interrupted the test because they had shown a fall

    in FEV1 [ 10 % with buffer solution. One hundredand three subjects were not considered because the

    temperature and humidity on the day when the test was

    carried out were not known. Only the first challenge of

    those few who had repeated the test several times was

    taken into consideration.

    These subjects were subdivided into subgroups on

    the basis of the PD20 value, sex, age, smoking habits,

    and BMI, in order

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