asthma is a chronic inflammatory disease of the airways characterized by bronchial hyperresponsiveness , variable airflow limitation , and symptoms such as dyspnea , wheezing , and cough , which improve spontaneously or with treatment .
the primary goals of asthma treatment include complete symptom control , optimal management of limitations in activities of daily living , and reducing future risks . 

1 
 2 
  most asthma patients have mild to moderate asthma , which is easily controlled with the use of inhaled corticosteroids ( ics ) alone or in association with a long - acting 2 agonist ( laba ) . 
 3 
  however , among patients with severe asthma
, there is a small subset of patients who remain symptomatic despite good adherence to treatment , correct use of inhalers , appropriate management of comorbidities , and use of high - dose ics in association with labas , oral corticosteroids , omalizumab , or any combination of the three . 

4 
 5 
  such patients are considered to have uncontrolled severe asthma ( ucsa ) , which , according to current asthma guidelines , should be treated at specialized centers . 

4 
 5 
  patients with ucsa require high - dose ics alone or in association with oral corticosteroids , the adverse effects of which include decreased protein synthesis and increased protein degradation and contribute to muscle atrophy . 
 6 
  in addition , increased airway resistance and lung hyperinflation
also contribute to reducing inspiratory muscle efficiency , resulting in increased muscle work and energy expenditure to overcome airflow limitation . 

7 
  the aforementioned factors have yet to be well studied in patients with ucsa .  
the six - minute walk test ( 6mwt ) is a submaximal exercise test that evaluates the overall and integrated responses of all body systems involved in physical exercise , including the pulmonary system , the cardiovascular system , peripheral and systemic circulation , blood , neuromuscular units , and muscle metabolism . 

8 
 9 
  respiratory muscle strength can be estimated from airway pressures generated by respiratory muscle contraction .
maximal static respiratory pressures are usually measured at the mouth during inhalation and exhalation , the former being designated mip and the latter being designated mep . 

10 
  the role of the 6mwt in the evaluation and follow - up of patients with copd , interstitial lung disease , pulmonary arterial hypertension , and heart failure is well established . 
 8 
  however , the only study evaluating the impact of severe asthma on the six - minute walk distance ( 6mwd ) in adults was a study conducted by canuto et al . , 
 11 
  who found that the 6mwd was significantly shorter in patients with difficult - to - control asthma ( dca ) using oral corticosteroids than in healthy controls .
in addition , although respiratory muscle strength ( particularly mip ) has been reported to be reduced in several studies involving asthma patients , it has yet to be evaluated in patients with ucsa . 

12 
  the primary objective of the present study was to evaluate respiratory muscle strength and 6mwt variables in patients with ucsa .
secondary objectives were to evaluate the impact of oral corticosteroid use on respiratory muscle strength and to determine the correlation of the level of physical activity with the 6mwd and the level of asthma control in such patients .
this was a cross - sectional study of ucsa patients over 18 years of age treated at the difficult - to - control asthma outpatient clinic of the federal university of minas gerais hospital das clnicas , in the city of belo horizonte , brazil , between september and december of 2012 .
the research project was approved by the research ethics committee of the federal university of minas gerais ( etic ruling no .
the diagnosis of severe asthma was based on the american thoracic society / european respiratory society ( ats / ers ) criteria , 
 13 
  as follows :  
 major criteria - use of oral corticosteroids for at least six months per year and continuous use of high - dose ics (  1,600 g of budesonide or equivalent ) in association with labasminor criteria - fev1 of < 80% ; pef variability > 20% ; daily use of short - acting 2 agonists ; use of more than three courses of oral corticosteroids per year ; history of near - fatal asthma ; one or more emergency room visits in the previous year ; and rapid decline in lung function after a decrease in the dose of corticosteroid therapy 
  major criteria - use of oral corticosteroids for at least six months per year and continuous use of high - dose ics (  1,600 g of budesonide or equivalent ) in association with labas minor criteria - fev1 of < 80% ; pef variability > 20% ; daily use of short - acting 2 agonists ; use of more than three courses of oral corticosteroids per year ; history of near - fatal asthma ; one or more emergency room visits in the previous year ; and rapid decline in lung function after a decrease in the dose of corticosteroid therapy the patients who were included in the present study received outpatient treatment for at least six months in order to control environmental factors and comorbidities , as well as to improve inhaler technique and treatment adherence . in addition , we included only patients assigned to global initiative for asthma ( gina ) and brazilian thoracic association ( bta ) asthma treatment step 4 or 5 ( labas / high - dose ics plus oral corticosteroids , anti - ige treatment , or both ) 
 1 
 2 
  and meeting two major ats / ers criteria or one major and two minor ats / ers criteria . 
 13 
  we excluded patients with severe heart disease ; current smokers ; former smokers who had a smoking history  10 pack - years or who had quit smoking less than one year prior ; and patients who had had exacerbations requiring emergency room treatment / hospitalization , use of prednisone or equivalent at doses above 20 mg , use of antibiotics , or any combination of the three in the last four weeks .  
the 6mwt was performed in a 25.6-m corridor with the use of a portable oximeter ( nonin medical , inc . ,
plymouth , mn , usa ) , in accordance with the recommendations of the ats . 

14 
  each of the participants underwent two 6mwts , at least 30 min apart .
we evaluated the following parameters : spo2 , as measured by pulse oximetry ; hr ; rr ; and patient perception of dyspnea and leg fatigue , as assessed by borg scale scores at the beginning and end of each test . in addition
, we determined the percentage of the predicted maximal hr ( % hrmax ) for adults , hr recovery at one minute after completion of the 6mwt ( hrr1 ) , and the 6mwd .
values of desaturation  4% , 
 8 
 14 
  % hrmax > 85% of predicted , 
 8 
 14 
  and hrr1 > 12 bpm were considered significant . 

15 
 17 
  the 6mwt during which the longest 6mwd was covered was considered valid ; absolute and percent predicted 6mwd values were calculated by the reference equation for the 6mwd in the brazilian population . 
 18 
  spirometry was performed with a koko spirometer ( pds instrumentation inc . , louisville , co , usa ) .
the tests were performed and the results were interpreted in accordance with the bta guidelines . 

10 
  all post - bronchodilator test results were reported as absolute values and as percentages of predicted values , in accordance with pereira et al . 
 19 
  respiratory muscle strength was evaluated in accordance with the bta guidelines , 
 10 
  with a digital manometer ( warren e collins inc . ,
braintree , ma , usa ) , the signals being read and recorded through individual ducts . a 2-mm hole in the circuit prevented false measurements as a result of involuntary contractions of the cheeks .
20 
  the level of asthma control was assessed with the asthma control test ( act ) , previously validated for use in brazil , 
 21 
 23 
  a score of 25 points indicating clinical remission of symptoms or totally controlled asthma , a score of 20 - 24 points indicating adequately controlled asthma , and a score of < 20 points indicating uncontrolled asthma .  
the level of physical activity was measured with the short version of the international physical activity questionnaire ( ipaq ) , previously validated for use in brazil . 

24 
 25 
  the instrument consists of seven questions regarding the frequency ( in number of days per week ) and duration ( in number of minutes per day ) of vigorous physical activity , moderate physical activity , and walking activity . on the basis of their ipaq scores
, individuals are classified as very active , active , irregularly active , or sedentary . in the present study , we divided the participants into two major groups : the group of very active / active individuals and the group of irregularly active / sedentary individuals . 

24 
 25 
  all study participants underwent chest hrct for the differential diagnosis of other diseases , such as copd , bronchiectasis , and allergic bronchopulmonary aspergillosis .  
data analysis was performed with the statistical package for the social sciences , version 18 ( spss inc . , chicago , il , usa ) , and minitab software , version 16 ( minitab inc .
the shapiro - wilk test was used in order to evaluate the distribution of the data .
categorical variables were expressed as absolute and relative frequencies , and continuous variables were expressed as mean and standard deviation ( parametric distribution ) or as median and range ( nonparametric distribution ) .
the mann - whitney test was used in order to evaluate the difference between the 6mwd recorded for the patients with ucsa and that predicted for healthy individuals , as well as to evaluate the association of physical activity levels ( ipaq scores ) with the 6mwd , act scores , % hrmax , and hrr1 .
spearman 's correlation test and the kruskal - wallis test were used in order to evaluate the association of oral corticosteroid use with mip and mep .
values of p < 0.05 were considered statistically significant . on the basis of the longest 6mwd found in the literature ( with a standard deviation of 90.44 m ) and using a level of significance of 0.05 and an unpaired two - tailed student 's t - test
, we estimated that a sample size of 26 was needed in order to detect a difference of 50 m between the 6mwd found in the present study and that found in the literature . 

three patients were excluded because of a probable overlap between asthma and copd , and another one was excluded because of asthma exacerbation during the month of data collection .   the final sample consisted of 25 asthma patients ( 18 females and 7 males ) , their mean age being 49 years and their mean body mass index being 28.9  7.9 kg / m ( table 1 ) . all patients had act scores of < 15 points , 14 ( 56% ) were classified as being irregularly active / sedentary , and 20 ( 80% ) had exercise limitation in the period between asthma attacks .
ten patients ( 40% ) had a history of exacerbations requiring icu admission , and 7 ( 28% ) had a history of exacerbations requiring mechanical ventilation .  

table 1.baseline characteristics of the uncontrolled severe asthma patients studied.acharacteristicn = 25age , years 
 49.8  12.6female gender18 ( 72)bmi , kg / m 
 28.9  7.9former smokers 
 4 ( 16)activity limitations in the period between attacksno limitations0 ( 0)limitations in exercise performance20 ( 80)limitations in activities of daily living3 ( 12)limitations in self - care2 ( 8)limitations at rest0 ( 0)attacks in the previous year 
 5 ( 0 - 23)systemic corticosteroid use during attacks (  4 courses / year)9 ( 36)continuous oral corticosteroid use6 ( 24)total number of hospitalizations 
 15 ( 0 - 100)icu admissions10 ( 40)need for mechanical ventilation7 ( 28)history of cpa1 ( 4)comorbidities21 ( 84)chronic rhinosinusitis22 ( 88)nasal polyposis2 ( 8)gerd13 ( 52)obesity11 ( 44)sah2 ( 8)diabetes mellitus4 ( 16)psychiatric disorder4 ( 16)copd2 ( 8)sequelae of tuberculosis1 ( 4)abpa1 ( 4)act 
 14.0  3.9physical activities - ipaq score 
 active or very active11 ( 44)irregularly active or sedentary14 ( 56)bmi : body mass index ; cpa : cardiopulmonary arrest ; gerd : gastroesophageal reflux disease ; sah : systemic arterial hypertension ; abpa : allergic bronchopulmonary aspergillosis ; act : asthma control test ; and ipaq : international physical activity questionnaire . avalues expressed as n ( % ) , except where otherwise indicated .
cindividuals who had a smoking history of = 10 packyears at the time of smoking cessation or those who had quit smoking at least one year prior .
bmi : body mass index ; cpa : cardiopulmonary arrest ; gerd : gastroesophageal reflux disease ; sah : systemic arterial hypertension ; abpa : allergic bronchopulmonary aspergillosis ; act : asthma control test ; and ipaq : international physical activity questionnaire .
cindividuals who had a smoking history of = 10 packyears at the time of smoking cessation or those who had quit smoking at least one year prior .
all patients were receiving treatment with labas and high - dose ics (  1,600 g of budesonide or equivalent ) , 6 ( 24% ) had been using at least 10 mg / day of prednisone for more than one year , and 3 ( 12% ) were using omalizumab .  
the most common ct findings were bronchiectasis that was minimal / moderate and predominantly central , in 3 patients ; small areas of centrilobular emphysema , in 11 ; mild right upper lobe fibrosis / atelectasis , in 1 ; and air trapping , in 1 .  
there was a predominance of obstructive lung disease ( mean fev1 , 58.8  21.8% of predicted ) , and 17 patients ( 68% ) had positive bronchodilator test results .
although mean mip and mep were normal , 7 ( 28% ) and 11 ( 44% ) of the 25 patients studied had reduced mip and mep ( of < 65% of predicted ) , respectively ( table 2 ) . of the 7 patients who had reduced mip , only 2 had spirometric signs of lung hyperinflation .  

table 2.spirometry results and maximal respiratory pressures in the uncontrolled severe asthma patients studied ( n = 25).avariableresultpre - bdpost - bdfev1,% of predicted58.8  21.8 66  22.4fev1 , l1.61  0.63 1.81  0.62fvc , % of predicted83.4  20.7 91.0  19.1fvc , l2.79  0.71 3.05 
0.65fev1/fvc56.3  12.0mip , cmh2o87.2  21.0mip , % of predicted72.9 15.2mep , cmh2o108.3  42.9mep , % of predicted67.6  22.2bd : bronchodilator .
avalues expressed as mean  sd . there was no significant difference ( p = 0.14 ) between the median 6mwd recorded for the ucsa patients in the present study-512 m ( range , 307.2 - 597.3 m)-and that predicted for healthy individuals-534 m ( range , 382.6 - 621.3 m)-(figure 1 ) .  

figure 1.distribution of the six - minute walk distance ( 6mwd ) in 25 patients with uncontrolled severe asthma ( 6mwd - ucsa ) in comparison with the 6mwd predicted for healthy adults in brazil ( 6mwd - ha).(18)a * outliers .
none of the patients required supplemental oxygen and there was no significant decrease in mean spo2 during the 6mwt ; however , 5 patients experienced desaturation during the test . of those , 2 experienced bronchospasm , which was reversed with the use of a short - acting 2 agonist , 2 had comorbidities ( allergic bronchopulmonary aspergillosis and sequelae of pulmonary tuberculosis ) , and 1 had evidence of emphysema and air trapping on chest ct scans . at the end of the 6mwt ,
table 3.six-minute walk test in the uncontrolled severe asthma patients studied ( n = 25).avariablebefore the 6mwtafter the 6mwtspo2 , % 96.1  1.193.7  3.5hr , bpm81.8  16.7117.8  20.3rr , breaths / min18.5  2.630.4  5.5borg scale score ( leg fatigue)0.1  0.42.9  2.6borg scale score ( dyspnea)0.9  1.24.7  1.96mwd , m-512  4.2hrr1 , bpm-21.7  8.3hrmax , % -71  116mwt : six - minute walk test ; 6mwd : six - minute walk distance ; hrr1 : hr recovery at one minute after completion of the 6mwt ; and hrmax : predicted maximal hr .
6mwt : six - minute walk test ; 6mwd : six - minute walk distance ; hrr1 : hr recovery at one minute after completion of the 6mwt ; and hrmax : predicted maximal hr .
when we compared the subset of patients treated with continuous oral corticosteroids or four or more courses of oral corticosteroids per year ( n = 15 ) with that of those treated with three or fewer ( n = 10 ) , in order to investigate the association between the frequency of oral corticosteroid use and respiratory muscle strength , we found no statistically significant differences in median mip-74.5% ( range , 59.0 - 104.0% ) and 72.5% ( range , 43.0 - 104.0% ; p = 0.15 ) , respectively - or mep-67.5% ( range , 29.0 - 121.0% ) and 63.5% ( range , 34.0 - 121.0% ; p = 0.45 ) , respectively .  
the 11 most physically active patients and the 14 least physically active patients were found to be similar in terms of their act scores , 6mwd , hrr1 , and % hrmax during the 6mwt ( table 4 ) .  

table 4.association of the level of physical activity with the level of asthma control and six - minute walk test variables in the uncontrolled severe asthma patients studied ( n = 25).avariablelevel of physical activity ( ipaq score)pvery active or activeirregularly active or sedentary(n = 11)(n = 14)6mwd , m537.6 ( 320.0 - 597.3)490.0 ( 307.2 - 588.6)0.308hrr1 , bpm19.0 ( 11.0 - 37.0)19.5 ( 10.0 - 36.0)0.935hrmax , % 72 ( 53 - 89)73 ( 50 - 84)0.621act score15 ( 7 - 17)13 ( 6 - 24)0.144ipaq : international physical activity questionnaire ; 6mwd : six - minute walk distance ; hrr1 : hr recovery at one minute after completion of the six - minute walk test ; hrmax : predicted maximal hr ; and act : asthma control test .
ipaq : international physical activity questionnaire ; 6mwd : six - minute walk distance ; hrr1 : hr recovery at one minute after completion of the six - minute walk test ; hrmax : predicted maximal hr ; and act : asthma control test .
patients who do not achieve asthma control at gina asthma treatment step 4 or 5 have historically been classified as having dca . 
 1 
 
however , debate over the most appropriate terminology has been ongoing for more than two decades because of the different criteria used in order to define severe asthma , dca , refractory asthma , therapy - resistant asthma , and , more recently , ucsa .   in 2000 , the ats proposed criteria for defining dca , and those criteria contributed to resolving part of the controversy . 
 13 
  however , it was only after the publication of the 2013 ats / ers task force guidelines - ratified and cited in the 2014 gina guidelines - that the classification of severe asthma became clearer . 
 4 
 5 
  according to the aforementioned guidelines , the term " difficult - to - treat asthma " should be reserved for asthma in patients who are able to achieve better disease control after improving environmental hygiene , inhaler technique , treatment adherence , or comorbidity management . however , the same guidelines defined patients with " severe asthma " as those who , despite the aforementioned measures , required drugs assigned to gina asthma treatment steps 4 and 5 in the last 12 months or systemic corticosteroids for at least 6 months in the last 12 months in order to maintain asthma control or those in whom the disease remained inadequately controlled despite treatment . 

4 
 5 
  patients defined as having ucsa are those who , in addition to having poorly controlled asthma , meet at least one of the following criteria 
 4 
 5 
 : an act score of < 20 points or an equivalent score on any other validated instrument for assessing asthma control ; two or more exacerbations requiring systemic corticosteroid use in the last year ; severe exacerbation requiring hospitalization in the last year ; and persistent airflow limitation despite gina asthma treatment step 4 or 5 . 
 4 
 5 
  therefore , it is increasingly important to characterize ucsa patients and identify outcomes that can aid in evaluating the impact of interventions on such patients . among such outcomes
the 6mwd recorded for the patients with ucsa was similar to that predicted for healthy brazilians . 

18 
  in addition , the patients with ucsa had normal post-6mwt spo2 , hrr1 , and respiratory muscle strength .  
it is known that the 6mwt provides indicators of functional capacity ( the 6mwd ) , pulmonary gas exchange ( spo2 ) , cardiovascular stress ( hr ) , cardiac automaticity ( hrr1 ) , and sensory stress ( dyspnea scores ) . 

8 
  although our patients were irregularly active or sedentary and had moderate obstructive lung disease and uncontrolled asthma , their mean 6mwd was 512  72 m. in addition , mean desaturation was less than significant during the test ( spo2 having decreased < 4% from baseline ) .  
we found that % hrmax was achieved in approximately 71% of the study participants , a finding that indicates efficient gas exchange and adequate cardiovascular stress .
mean hrr1 ( 21.7  8.3 bpm ) was significant , suggesting normal cardiac automaticity , although perceived leg fatigue and perceived dyspnea after completion of the 6mwt were moderate and somewhat strong , respectively .
after reviewing the literature , we found only one study evaluating adults with severe asthma during the 6mwt . 

11 
  in that study , the 6mwd was significantly shorter in the group of patients with dca than in the controls . 

11 
  however , the mean 6mwd in the group of patients with dca was 435 m , 
 11 
  which is approximately 112 m shorter than the 6mwd recorded for our sample of patients with ucsa .
it is of note that the patients in that study were older than those in the present study ( 52.3  8.3 years vs. 49.8  14.4 years ) , had more severe obstruction , as shown by percent predicted fev1 ( 44.0  15.9% vs. 58.8  21.8% ) , and used drugs that were more potent , such as oral corticosteroids ( 64% vs. 24% ) and omalizumab ( 47% vs. 12% ) .   at the end of the 6mwt , there was a decrease in spo2 in 5 of the 25 ucsa patients investigated in the present study . in 2 ,
this was attributed to bronchospasm , which was rapidly reversed by rest and by using short - acting 2 agonists .
the remaining 3 had comorbidities ( bronchiectasis due to sequelae of tuberculosis , allergic bronchopulmonary aspergillosis , and pulmonary emphysema with air trapping , respectively ) .
these results suggest that , in the absence of bronchospasm , the presence of desaturation during the 6mwt in patients with ucsa should raise the suspicion of comorbidities .   according to one group of authors , 

27 
  the reasons for exercise limitation in patients with ucsa should be investigated and include asthma itself , alveolar hyperventilation , exercise - induced bronchoconstriction , physical deconditioning , submaximal test , and cardiac ischemia .
the authors noted that , after the reasons for exercise limitation have been identified , treatment can be revised , particularly the use of high - dose corticosteroids in patients without pulmonary limitation . 
 27 
  respiratory muscle strength measurements ( mean mip and mep ) in the ucsa patients investigated in the present study were no different from those in healthy individuals .
an increase in functional residual capacity ( caused by lung hyperinflation ) flattens the diaphragm and alters respiratory mechanics , resulting in a mechanical disadvantage , which can be inferred by a reduction in respiratory muscle strength . 

7 
 28 
  however , asthma patients with mild or moderate obstructive lung disease might not have significant lung hyperinflation resulting in changes in diaphragm position . 

29 
 30 
  the fact that the patients in the present study had moderate airway obstruction might explain why their mips and meps were similar to those in healthy individuals .  
we found no significant differences in mean mip and mep between the asthma patients who often used oral corticosteroids and those who did not ( i.e. , those who were treated with three or fewer courses of oral corticosteroids per year ) .
one group of authors found that inspiratory muscle strength was lower in oral corticosteroid - dependent asthma patients than in asthma patients using high - dose ics , the level of lung hyperinflation being similar between the two groups of patients . 

28 
  it should be noted that mip and mep were found to be reduced in 28% and 48% of the patients , respectively .
a reduction in respiratory muscle strength can occur , particularly in obese females , as a result of respiratory muscle dysfunction .
respiratory muscle activity can also be negatively affected by increased elastic resistance caused by the presence of excess adipose tissue in the rib cage and abdomen , which results in a mechanical disadvantage to the muscles . 

31 
 32 
  in our study , 72% of the patients were female , their mean body mass index being 28 kg / m .  
although the results of the present study should be interpreted with caution , particularly because of the lack of a control group , the small sample size , the cross - sectional study design , and the single - center nature of the study , they are relevant because of the lack of studies examining exercise capacity in patients with severe asthma and because of the difficulties in investigating exercise capacity in such patients . in addition , the present study is relevant because it examined a sample of patients treated at a referral center in a university hospital and because of its high statistical power ( of 81% ) .   in conclusion ,
the 6mwd recorded for the ucsa patients in the present study was found to be similar to that predicted for healthy brazilians .
the fact that there was a decrease in spo2 in 5 of the 25 patients studied can be explained by the presence of bronchospasm and comorbidities .
respiratory muscle strength measurements ( mean mip and mep ) were found to be above the predicted lower limit , regardless of the use of oral corticosteroids .
further studies , involving a larger number of patients and including a control group , are needed in order to gain a better understanding of exercise capacity in patients with severe asthma and determine its role in the management of the disease .
  avaliar a fora muscular respiratria e variveis obtidas no teste de caminhada de seis minutos ( tc6 ) em pacientes com asma grave no controlada ( agnc ) .
os pacientes foram submetidos a tc6 , espirometria e medidas da fora muscular respiratria e responderam o asthma control test ( act , teste de controle da asma ) .
o teste de mann - whitney foi utilizado na anlise das variveis do tc6 , e o teste de kruskal - wallis foi utilizado na verificao de uma possvel associao do uso de corticoide oral com a fora muscular respiratria .
  foram includos 25 pacientes , com mdias de vef1 de 58,8  21,8% do previsto e escore do act de 14,0  3,9 pontos .
no houve diferena significativa entre a mediana da distncia percorrida no tc6 dos pacientes com agnc e aquela prevista para brasileiros saudveis ( 512 m e 534 m , respectivamente ; p = 0,14 ) .
durante o tc6 , no houve queda significativa da spo2 . as mdias de pimx e pemx foram normais ( 72,9  15,2% e 67,6  22,2% , respectivamente ) .
no houve diferenas significativas nas medidas de pimx ( p = 0,15 ) e pemx ( p = 0,45 ) entre os pacientes que usavam ao menos quatro ciclos de corticoide oral por ano e os que o usavam por trs ou menos ciclos por ano .
  nossos achados sugerem que os pacientes com agnc so semelhantes a indivduos normais em termos das variveis do tc6 e da fora muscular respiratria .
a asma  uma doena inflamatria crnica das vias areas , caracterizada por hiper - reatividade brnquica , limitao varivel do fluxo areo e sintomas , como dispneia , chiado e tosse , que melhoram espontaneamente ou com tratamento .
os objetivos bsicos do manejo da asma so o controle total dos sintomas e das limitaes das atividades dirias e a reduo dos riscos futuros . 
 1 
 2 
 a maioria dos pacientes tem asma leve ou moderada , facilmente controladas com o uso de corticoides por via inalatria ( ci ) de forma isolada ou associados com long - acting 2 agonist ( laba , 2-agonista de longa durao )
. 
 3 
  entretanto , entre os asmticos graves , h um pequeno subgrupo de pacientes que permanecem sintomticos apesar de boa adeso ao tratamento , uso correto dos dispositivos , manejo adequado de comorbidades e uso de altas dosagens de ci associados com laba e / ou corticoide oral e / ou omalizumabe . 
 4 
 5 
  esta condio particular  denominada asma grave no controlada ( agnc ) , a qual , segundo as diretrizes atuais de asma , deve ser tratada em servios especializados . 

4 
 5 
  pacientes com agnc necessitam de altas doses de ci associados ou no a corticoides orais , os quais tm , entre seus efeitos adversos , a reduo da sntese de protenas e o aumento de sua degradao , efeitos esses que contribuem para a atrofia muscular . 
 6 
 adicionalmente , o aumento da resistncia das vias areas e da hiperinsuflao pulmonar tambm contribuem para a reduo da eficincia de msculos inspiratrios , resultando em maior trabalho muscular e maior gasto energtico para vencer a limitao ao fluxo areo . 
 7 
  esses fatores ainda no foram bem estudados na agnc .
o teste de caminhada de seis minutos ( tc6 )  um teste submximo que prov uma avaliao da resposta global e integrada de todos os aspectos corporais envolvidos na realizao do exerccio ( sistema pulmonar , sistema cardiovascular , circulao sistmica e perifrica , sangue , unidade neuromuscular e metabolismo muscular ) . 

8 
 9 
 j a fora muscular respiratria pode ser estimada a partir das presses geradas nas vias areas pela contrao dos msculos respiratrios . as presses respiratrias estticas mximas so habitualmente medidas ao nvel da boca na inspirao ( pimx ) e na expirao ( pemx ) . 

10 
  o papel do tc6 na avaliao e no acompanhamento de pacientes com dpoc , doena intersticial pulmonar , hipertenso arterial pulmonar e insuficincia cardaca est bem estabelecido . 
 8 
 no entanto , em adultos , o impacto do comprometimento na asma grave foi avaliado apenas em um estudo de canuto et al . , 
 11 
  que verificaram uma distncia percorrida no tc6 ( dtc6 ) significativamente menor nos pacientes com asma de difcil controle ( adc ) , em uso de corticoide oral , quando comparados com indivduos saudveis do grupo controle .
por outro lado , embora a reduo da fora muscular , principalmente da pimx , tenha sido descrita em vrios estudos com pacientes asmticos , a mesma ainda no foi avaliada no grupo de pacientes com agnc . 
 12 
  o objetivo principal do presente estudo foi investigar o comportamento das variveis do tc6 , assim como pimx e pemx , em pacientes com agnc .
de forma secundria , objetivamos investigar o impacto do uso de corticoide oral na fora muscular respiratria e a correlao do nvel de atividade fsica dos pacientes com a dtc6 e o nvel de controle da asma .
trata - se de estudo transversal que incluiu pacientes maiores de 18 anos com asma grave acompanhados no ambulatrio de asma de difcil controle do hospital das clnicas da universidade federal de minas gerais ( ufmg ) , em belo horizonte ( mg ) , no perodo entre setembro e dezembro de 2012 . o projeto foi aprovado pelo comit de tica em pesquisa da ufmg ( parecer etic n 156.403/2012 ) .
todos os participantes assinaram o termo de consentimento livre e esclarecido .   o diagnstico de asma grave baseou - se nos critrios da american thoracic society / european respiratory society ( ats / ers ) , 
 13 
  assim definidos : como critrios maiores , uso de corticoide oral por no mnimo seis meses no ano e uso contnuo de ci em doses elevadas (  1.600 g de budesonida ou equivalente ) associado a laba ; como critrios menores , vef1 < 80% ; variabilidade
do pfe > 20% ; uso dirio de 2-agonista de curta durao ; uso de mais de trs cursos de corticoide oral no ano ; histria de episdio de asma quase fatal ; uma ou mais consultas em servios de urgncia no ano anterior ; e deteriorao rpida da funo pulmonar ao diminuir a dose do tratamento com corticoide .
os pacientes includos tiveram acompanhamento ambulatorial por , no mnimo , seis meses , visando o controle de fatores ambientais e de comorbidades , a melhora da tcnica de uso dos dispositivos inalatrios e o aumento da adeso ao tratamento .
alm disso , foram includos apenas os pacientes nas etapas 4 e 5 de tratamento da asma ( laba /
ci em dose elevada mais corticoide oral e / ou anti - ige ) segundo as diretrizes da global initiative for asthma ( gina ) 
 1 
  e da sociedade brasileira de pneumologia e tisiologia ( sbpt ) , 
 2 
  e com dois critrios maiores ou um critrio maior e dois menores dos critrios da ats / ers . 

13 
  foram excludos os pacientes com cardiopatia grave ; fumantes ativos ; ex - fumantes com carga tabgica  10 maos - ano ou que cessaram tabagismo h menos de um ano ; e pacientes que tiveram exacerbao necessitando de atendimento em pronto - socorro / internao , uso de prednisona ou equivalente acima de 20 mg e / ou de antibiticos nas ltimas quatro semanas .   o tc6 foi realizado em um corredor de 25,6 m utilizando um oxmetro porttil ( nonin medical , inc . , plymouth , mn , eua ) , seguindo as recomendaes da ats . 
 14 
 todos os pacientes fizeram dois tc6 , com um intervalo mnimo de 30 min entre eles .
foram avaliados os seguintes parmetros : spo2 medida por oximetria de pulso , fc , fr , e percepo da intensidade de dispneia e de fadiga nos membros inferiores pela escala de borg ao incio e ao final dos testes .
foram verificados tambm o valor percentual da fc em relao  fc mxima prevista para adultos ( % fcmx ) , a fc de recuperao no primeiro minuto aps o trmino do teste ( fcr1 ) e a dtc6 .
foram considerados significativos valores de dessaturao  4% , % fcmx > 85% do previsto 
 8 
 14 
 e fcr1 > 12 bpm
. 
 15 
 17 
  considerou - se vlido o tc6 com o maior valor para dtc6 ; os valores absolutos e percentuais do previsto para a dtc6 foram calculados atravs da equao de referncia para tc6 da populao brasileira . 

18 
  a espirometria foi realizada utilizando um espirmetro da marca koko ( pds instrumentation inc . , louisville , co , eua ) .
10 
  os valores encontrados no teste ps - broncodilatador foram relatados como valores absolutos e percentuais em relao aos valores previstos de acordo com pereira et al . 

19 
  a fora dos msculos respiratrios foi avaliada atravs de um manovacumetro digital ( warren e collins inc . , braintree , ma , eua )
seguindo as diretrizes nacionais da sbpt , 
 10 
  com leitura e armazenamento dos sinais atravs de ductos individuais . um orifcio de 2 mm no circuito impedia falsas medidas por contrao involuntria das bochechas .
a pimx foi mensurada ao nvel do vr , e a pemx foi mensurada ao nvel da cpt .
os resultados foram expressos em cmh2o . 
 20 
  o nvel de controle da asma foi avaliado atravs do asthma control test ( act , teste de controle da asma ) , no qual 25 pontos representam remisso clnica dos sintomas ou controle total da asma ; de 20 a 24 pontos , controle adequado da doena ; e abaixo de 20 pontos , asma no controlada ; foi utilizada a verso validada para uso no brasil . 
 21 
 23 
  o nvel de atividade fsica foi medido de acordo com international physical activity questionnaire ( ipaq , questionrio internacional de atividade fsica ) , verso curta , validado para uso no brasil . 

24 
 25 
  o instrumento contm sete questes relacionadas  frequncia , em dias por semana , e  durao , em minutos por dia , das atividades fsicas vigorosas , moderadas e de caminhada .
o escore classifica os indivduos em muito ativo , ativo , irregularmente ativo e sedentrio .
agrupamos as classificaes em dois grupos : muito ativo ou ativo e irregularmente ativo ou sedentrio . 

24 
 25 
  todos os pacientes do estudo realizaram tcar de trax para o diagnstico diferencial de outras doenas associadas , como dpoc , bronquiectasias e aspergilose broncopulmonar alrgica . a anlise dos dados foi realizada no statistical package for the social sciences , verso 18 ( spss inc . ,
chicago , il , eua ) e minitab , verso 16 ( minitab inc . , state college , ma , eua ) .
o teste de shapiro - wilk foi utilizado para avaliar a distribuio dos dados . as variveis categricas foram apresentadas em frequncia e proporo ,
e as variveis contnuas foram expressas como mdia e desvio - padro ( distribuio paramtrica ) ou como mediana e variao ( distribuio no paramtrica ) .
para avaliar a diferena entre a dtc6 nos pacientes com agnc e o valor previsto da dtc6 em indivduos normais , assim como para verificar a associao da prtica de atividade fsica ( ipaq ) com as variveis dtc6 , escore do act , % fcmx e fcr1 , foi utilizado o teste de mann - whitney . a possvel associao entre o uso
de corticoide oral com pimx e pemx foi avaliada atravs do teste de correlao de spearman e teste de kruskal - wallis .
com base na maior dtc6 encontrada na literatura , considerando - se um desvio - padro de 90,44 m , nvel de significncia de 0,05 , usando - se o teste t de student bicaudal para uma amostra nica , o tamanho da amostra foi estimado em 26 pacientes para se verificar uma diferena de
trs indivduos foram excludos por se tratarem de pacientes com provvel sndrome de sobreposio asma / dpoc , e outro foi excludo devido a exacerbao da asma durante o ms da coleta dos dados .  
participaram 25 pacientes asmticos ( 18 do sexo feminino e 7 do sexo masculino ) , com mdia de idade de 49 anos e mdia de ndice de massa corprea de 28,9  7,9
todos os pacientes apresentaram escores do act < 15 pontos , 14 pacientes ( 56% ) eram irregularmente ativos / sedentrios , e 20 ( 80% ) tinham limitaes para exerccios no perodo intercrise .
dez pacientes ( 40% ) tinham histria de exacerbao com internao em terapia intensiva , e 7 ( 28% ) , com necessidade de ventilao mecnica . 

tabela 1.caractersticas basais dos pacientes com asma grave no controlada.acaractersticasn = 25idade , anos 
 49,8  12,6sexo feminino18 ( 72)imc , kg / m 
 28,9  7,9ex - fumantes 
 4 ( 16)limitaes das atividades na intercrisesem limitaes0 ( 0)no exerccio20 ( 80)nas atividades dirias3 ( 12)nos cuidados pessoais2 ( 8)em repouso0 ( 0)presena de crises no ltimo ano 
 5 ( 0 - 23)uso de ct sistmico nas crises (  4 ciclos / ano)9 ( 36)uso de ct oral contnuo6 ( 24)total de internaes 
 15 ( 0 - 100)internaes em uti10 ( 40)necessidade de ventilao mecnica7 ( 28)histria de pcr1 ( 4)comorbidades21 ( 84)rinossinusite crnica22 ( 88)polipose nasal2 ( 8)drge13 ( 52)obesidade11 ( 44)has2 ( 8)diabetes mellitus4 ( 16)distrbio psiquitrico4 ( 16)dpoc2 ( 8)sequela de tuberculose1 ( 4)abpa1 ( 4)act 
 14,0  3,9atividades fsicas - ipaq 
 ativo ou muito ativo11 ( 44)irregularmente ativo ou sedentrio14 ( 56)mc : ndice de massa corprea ; ct : corticosteroide ; pcr : parada cardiorrespiratria ; drge : doena do refluxo gastroesofgico ; has : hipertenso arterial sistmica ; abpa : aspergilose broncopulmonar alrgica ; act : asthma control test ; e ipaq : international physical activity questionnaire .
. cconsiderado como o indivduo que cessou o tabagismo com carga tabgica = 10 anosmao ou que cessou o tabagismo h pelo menos um ano .
mc : ndice de massa corprea ; ct : corticosteroide ; pcr : parada cardiorrespiratria ; drge : doena do refluxo gastroesofgico ; has : hipertenso arterial sistmica ; abpa : aspergilose broncopulmonar alrgica ; act : asthma control test ; e ipaq : international physical activity questionnaire .
cconsiderado como o indivduo que cessou o tabagismo com carga tabgica = 10 anosmao ou que cessou o tabagismo h pelo menos um ano .
todos os pacientes estavam em uso de laba e dose alta de ci (  1.600 g de budesonida ou equivalente ) , 6 ( 24% ) usavam pelo menos 10 mg / dia de prednisona h mais de um ano , e 3 ( 12% ) utilizavam omalizumabe .   as principais alteraes tomogrficas foram bronquiectasias
mnimas / moderadas com predomnio central , em 3 pacientes ; pequenas reas de enfisema centrolobular , em 11 ; fibroatelectasia discreta do lobo superior direito , em 1 ; e aprisionamento areo , em 1 .
houve predomnio de distrbio ventilatrio obstrutivo com mdia de vef1 de 58,8  21,8% do previsto , e 17 pacientes ( 68% ) tiveram prova broncodilatadora positiva . as mdias da pimx e pemx foram normais ; entretanto , 7 ( 28% ) e 11 ( 44% ) dos pacientes apresentaram pimx e pemx reduzidas ( < 65% do previsto ) , respectivamente ( tabela 2 ) .
dos 7 pacientes que tinham pimx reduzidas , somente 2 apresentaram sinais espiromtricos de hiperinsuflao pulmonar .  

tabela 2.resultados de espirometria e presses respiratrias mximas nos pacientes com asma grave no controlada ( n = 25).avariveisresultadospr - bdps - bdvef1,% predito58,8  21,8 66  22,4vef1 , l1,61  0,63 1,81  0,62cvf , % predito83,4  20,7 91,0  19,1cvf , l2,79
 0,71 3,05  0,65vef1/cvf56,3  12,0pimx , cmh2o87,2  21,0pimx , % predito72,9 15,2pemx , cmh2o108,3
no houve diferena significativa ( p = 0,14 ) entre os valores medianos da dtc6 - 512 m ( variao : 307,2 - 597,3 m ) - e da dtc6 prevista para indivduos normais - 534 m ( variao : 382,6 - 621,3 m ) - ( figura 1 ) .  

figura 1.distribuio da distncia percorrida no teste de caminhada de seis minutos no grupo de pacientes ( n = 25 ) com asma grave no controlada ( dtc6-agnc ) em comparao com a mesma distncia prevista para adultos brasileiros saudveis ( dtc6-as).(18)a * valores discrepantes .
nenhum paciente utilizou oxignio suplementar e no houve queda da spo2 mdia durante o tc6 ; porm , 5 pacientes apresentaram dessaturao durante o mesmo .
dentre esses , 2 apresentaram broncoespasmo , que foi revertido com a utilizao de 2-agonista de curta durao , 2 tinham comorbidades ( aspergilose broncopulmonar alrgica e sequela de tuberculose pulmonar ) , e 1 apresentara enfisema e aprisionamento areo na tc de trax .
ao final do tc6 , a intensidade da percepo da fadiga de membros inferiores foi leve e a de dispneia foi de leve a moderada .
tabela 3.teste de caminhada de seis minutos nos pacientes com asma grave no controlada ( n = 25).avariveis antes do tc6aps o tc6spo2 , % 96,1  1,193,7  3,5fc , bpm81,8  16,7117,8  20,3fr , ciclos / min18,5  2,630,4  5,5escala de borg ( fadiga membros inferiores)0,1  0,42,9  2,6escala de borg ( dispneia)0,9  1,24,7  1,9dtc6 , m-512  4,2fcr1 , bpm-21,7  8,3fcmx , % -71  11tc6 : teste de caminhada de seis minutos ; dtc6 : distncia percorrida no tc6 ; fcr1 : queda da fc no primeiro minuto aps o trmino do tc6 ; e fcmx : fc mxima prevista .
tc6 : teste de caminhada de seis minutos ; dtc6 : distncia percorrida no tc6 ; fcr1 : queda da fc no primeiro minuto aps o trmino do tc6 ; e fcmx : fc mxima prevista .
ao compararmos o subgrupo de pacientes em uso continuo de corticoide oral ou com quatro ou mais ciclos por ano ( n = 15 ) com o subgrupo de pacientes com trs ou menos ciclos por ano ( n = 10 ) a fim de investigar a associao entre a frequncia de uso de corticoide oral e a fora muscular respiratria , no encontramos diferenas estatisticamente significativas entre os valores medianos de pimx - 74,5% ( variao : 59,0 - 104,0% ) e 72,5% ( variao : 43,0 - 104,0% ; p = 0,15 ) , respectivamente - e pemx - 67,5% ( variao : 29,0 - 121,0% ) e 63,5% ( variao : 34,0 - 121,0% ; p = 0,45 ) , respectivamente .
os 11 pacientes mais ativos fisicamente e os 14 menos ativos apresentaram resultados semelhantes em relao a act , dtc6 , fcr1 e % fcmx no tc6 ( tabela 4 ) . 

tabela 4.associao do nvel de atividade fsica dos pacientes com asma grave no controlada ( n = 25 ) com o nvel de controle de asma e variveis do teste de caminhada de seis minutos.avariveisnvel de atividade fsica ( ipaq)pmuito ativo ou ativoirregularmente ativo ou sedentrio(n = 11)(n = 14)dtc6 , m537,6 ( 320,0 - 597,3)490,0 ( 307,2 - 588,6)0,308fcr1 , bpm19,0 ( 11,0 - 37,0)19,5 ( 10,0 - 36,0)0,935fcmx , % 72 ( 53 - 89)73 ( 50 - 84)0,621escore act15 ( 7 - 17)13 ( 6 - 24)0,144ipaq : international physical activity questionnaire ; dtc6 : distncia percorrida no teste de caminhada de seis minutos ; fcr1 : queda da fc no primeiro minuto aps o trmino do teste de caminhada de seis minutos ; fcmx : fc mxima prevista ; e act : asthma control test .
ipaq : international physical activity questionnaire ; dtc6 : distncia percorrida no teste de caminhada de seis minutos ; fcr1 : queda da fc no primeiro minuto aps o trmino do teste de caminhada de seis minutos ; fcmx : fc mxima prevista ; e act : asthma control test .
historicamente , os pacientes que no atingem o controle da asma , apesar do tratamento nas etapas 4 ou 5 segundo o gina , so classificados como portadores de adc . 
 1 
  entretanto , h mais de duas dcadas persistem muitas discusses sobre a terminologia mais apropriada devido aos diferentes critrios de definio utilizados para asma grave , adc , asma refratria ou resistente ao tratamento e , mais recentemente , agnc .  
em 2000 , uma publicao da ats sugeriu critrios de definio de adc , que ajudaram a reduzir parte dessas controvrsias . 
 13 
  no entanto , somente aps a publicao da fora tarefa da ats / ers em 2013 , ratificada e citada na diretriz gina de 2014 ,  que essa classificao tornou - se mais clara
. 
 4 
 5 
  de acordo com aquelas publicaes , o termo " asma difcil de tratar " deve ser reservado para os pacientes que melhoram o controle da asma aps medidas de higiene ambiental , melhora da tcnica de uso dos dispositivos , melhora da adeso ao tratamento ou manejo adequado de comorbidades .
por outro lado , as mesmas publicaes definiram " asma grave " como o grupo de pacientes que , apesar das medidas citadas anteriormente , necessitaram de medicamentos nas etapas 4 e 5 segundo gina nos ltimos 12 meses ou de corticoides sistmicos por , no mnimo , 6 meses nos ltimos 12 meses para manter o controle da asma ou que permaneceram sem um controle adequado apesar do tratamento . 
 4 
 5 
  cabe destacar ainda que os pacientes definidos como agnc seriam aqueles
que mantiveram pelo menos um dos critrios alm do baixo controle de sintomas 
 4 
 5 
 : act < 20 pontos ou resultados equivalentes em outro escore validado para a verificao do controle da asma ; duas ou mais exacerbaes , necessitando de corticoide sistmico no ltimo ano ; exacerbao grave com necessidade de internao no ltimo ano ; e persistncia de limitao do fluxo areo apesar do tratamento nas etapas 4 ou 5 segundo gina . 

4 
 5 
 portanto , torna - se cada vez mais importante a caracterizao de pacientes com agnc , bem como a identificao de desfechos que auxiliem na avaliao do impacto de intervenes nesses pacientes .
nesse contexto , inclui - se a capacidade de exerccio e a fora muscular respiratria .
no nosso estudo , os pacientes com agnc percorreram uma dtc6 semelhante quela prevista para a populao brasileira .
alm disso , eles apresentaram comportamento normal da spo2 mdia ao final do teste , reduo adequada da fc um minuto aps o trmino do tc6 e fora muscular respiratria normal .  
como se sabe , o tc6 fornece indicadores da capacidade funcional , por meio da dtc6 , da integridade da troca gasosa intrapulmonar pela spo2 , do estresse cardiovascular pela fc , da automao cardaca
pela fcr1 e do estresse sensorial pelos escores de dispneia . 
 8 
  em nosso estudo , os pacientes percorreram , em mdia , 512  72 m no tc6 , apesar de apresentarem padro obstrutivo moderado , serem irregularmente ativos ou sedentrios e apresentarem asma no controlada .
adicionalmente , no se observou dessaturao mdia significativa durante o teste ( queda da spo2 < 4% em relao aos valores basais ) .
aproximadamente 71% dos participantes atingiram a % fcmx , denotando uma troca gasosa eficiente e estresse cardiovascular satisfatrio . a mdia de
fcr1 ( 21,7  8,3 bpm ) foi significativa , sugerindo automao cardaca normal , o se que contrape com o achado de percepo da fadiga moderada e de dispneia ( um pouco forte ) ao final do teste .
aps revisarmos a literatura , encontramos apenas um estudo em adultos sobre o comportamento de pacientes com asma grave durante o tc6 . 
 11 
 naquele estudo , a dtc6 nos pacientes com adc foi significativamente menor em relao aos seus controles . 
 11 
  entretanto , a mdia da dtc6 no grupo com adc foi de 435 m , 
 11 
  aproximadamente 112 m inferior  dtc6 em nossa amostra .
cabe ressaltar que os pacientes daquele estudo eram mais velhos que os do presente estudo ( 52,3  8,3 anos vs. 49,8  14,4 anos ) , com maior grau de obstruo , indicado pelo vef1 em % do previsto ( 44,0  15,9% vs. 58,8  21,8% ) e faziam uso de mais medicamentos potentes , como corticoide oral ( 64% vs. 24% ) e omalizumabe ( 47% vs. 12% ) .  
em 2 pacientes essa queda foi atribuda a broncoespasmo , revertido rapidamente com repouso e uso de 2-agonistas de curta durao .
os outros 3 pacientes tinham comorbidades ( bronquiectasias devido a sequela de tuberculose , aspergilose broncopulmonar alrgica e enfisema pulmonar com aprisionamento areo , respectivamente ) .
esses resultados sugerem que , na ausncia de broncoespasmo , a presena de dessaturao durante o tc6 em pacientes com agnc deve alertar para a possibilidade de presena de comorbidades .  
para um grupo de autores , 
 27 
  a limitao ao exerccio em pacientes com agnc deve ser investigada quanto aos possveis fatores , como a prpria asma , hiperventilao alveolar , broncoconstrio induzida pelo exerccio , descondicionamento fsico , teste submximo e isquemia cardaca .
os autores observaram que , ao se identificarem os fatores limitantes , pode - se rever o tratamento , em especial o uso de altas doses de corticoide naqueles pacientes nos quais no foi encontrada limitao pulmonar . 

27 
  a medida da fora muscular respiratria ( pimx e pemx ) dos pacientes no presente estudo , em mdia , no foi diferente da observada em indivduos normais .
o aumento na capacidade residual funcional , causado pela hiperinsuflao pulmonar , retifica o diafragma e altera a mecnica respiratria , resultando em desvantagem mecnica , que pode ser inferida pela reduo da fora dos msculos respiratrios . 

7 
 28 
  entretanto , os asmticos com distrbio ventilatrio obstrutivo leve ou moderado podem no apresentar hiperinsuflao pulmonar significativa que altere a posio do diafragma . 

29 
 30 
 como os pacientes da presente casustica apresentavam obstruo moderada das vias areas ,  possvel que esse fato justifique a similaridade de seus valores de pimx e pemx com a de indivduos normais .
no encontramos diferenas significativas entre as mdias de pimx e pemx dos asmticos com uso frequente de corticoide oral com aqueles com uso infrequente ( trs ou menos ciclos por ano ) .
um grupo de autores relatou reduo da fora muscular inspiratria em asmticos dependentes de corticoides orais quando comparados com pacientes em uso de ci em altas doses e com graus semelhantes de hiperinsuflao pulmonar . 

28 
  deve - se ressaltar que 28% e 48% dos pacientes tiveram pimx e pemx reduzidas , respectivamente .
a fora muscular respiratria pode estar reduzida principalmente em mulheres obesas em consequncia de uma disfuno muscular respiratria .
a atividade muscular ventilatria pode ser tambm comprometida pelo aumento da resistncia elstica causada pelo excesso de tecido adiposo na caixa torcica e no abdome , o qual acarreta desvantagem mecnica aos msculos . 
 31 
 32 
  em nosso estudo , 72% das pacientes eram do sexo feminino , com mdia de ndice de massa corprea de 28 kg / m .
embora os resultados do presente estudo devam ser avaliados com cautela , principalmente devido  falta de um grupo controle ,  pequena casustica , ao delineamento transversal e por ter sido conduzido em um nico centro , os mesmos so relevantes devido  escassez e s dificuldades de pesquisa da capacidade de exerccio em pacientes com asma grave , assim como por representar uma amostra de um centro de referncia de um hospital universitrio e pelo alto poder estatstico observado ( poder do teste de 81% ) .  
em concluso , de acordo com a presente casustica , a dtc6 nos pacientes com agnc foi semelhante aos valores previstos para a dtc6 em indivduos normais no brasil .
a queda da spo2 em 5 pacientes pode ser explicada pela presena de broncoespasmo e de comorbidades . a mdia
das foras musculares respiratrias foi acima do limite inferior previsto , independente do uso de corticoide oral .
so necessrios novos estudos envolvendo um maior nmero de pacientes e com a incluso de um grupo controle para um maior entendimento do comportamento da capacidade de esforo em pacientes com asma grave e para a definio do seu valor no manejo dessa doena .
 objective : to evaluate respiratory muscle strength and six - minute walk test ( 6mwt ) variables in patients with uncontrolled severe asthma ( ucsa ) . methods : this was a cross - sectional study involving ucsa patients followed at a university hospital . 
 the patients underwent 6mwt , spirometry , and measurements of respiratory muscle strength , as well as completing the asthma control test ( act ) . 
 the mann - whitney test was used in order to analyze 6mwt variables , whereas the kruskal - wallis test was used to determine whether there was an association between the use of oral corticosteroids and respiratory muscle strength . 
 results : we included 25 patients . 
 mean fev1 was 58.8  21.8% of predicted , and mean act score was 14.0  3.9 points . 
 no significant difference was found between the median six - minute walk distance recorded for the ucsa patients and that predicted for healthy brazilians ( 512 m and 534 m , respectively ; p = 0.14 ) . during the 6mwt 
 , there was no significant drop in spo2 . 
 mean mip and mep were normal ( 72.9  15.2% and 67.6  22.2% , respectively ) . 
 comparing the patients treated with at least four courses of oral corticosteroids per year and those treated with three or fewer , we found no significant differences in mip ( p = 0.15 ) or mep ( p = 0.45 ) . 
 conclusions : our findings suggest that ucsa patients are similar to normal subjects in terms of 6mwt variables and respiratory muscle strength . 
 the use of oral corticosteroids has no apparent impact on respiratory muscle strength . 
Introduction
Methods
Results
Discussion
OBJETIVO:
MTODOS:
RESULTADOS:
CONCLUSES:
Introduo
Mtodos
Resultados
Discusso