36 Annals oftheRhewatic Diseases 1991; 50: 36-40 Bronchial hyperresponsiveness to methacholine in Ann Rheum Dis: first published as 10.1136/ard.50.1.36 on 1 January 1991. Downloaded from patients with primary Sjogren's syndrome Bjorn Gudbjornsson, Hans Hedenstrom, Gunnemar Stalenheim, Roger Hallgren Abstract inhalation in a consecutive series of patients The prevalence of bronchial hyperresponsive- with primary Sjogren's syndrome. We found ness (BHR) to methacholine inhalation in a that most patients were hyperreactive in the consecutive series of 21 patients with primar test, and we correlated the methacholine test Sj6gren's syndrome was studied prospectively. findings with clinical features and spirometric Slight to severe BHR was seen in 12/20 (60%/o) findings. of the patients. Ten of 12 patients with BHR (83%) had a non-productive cough, wheezing, or intermittent breathlessness. Bronchial Patients and methods hyperresponsiveness was more common in A consecutive, non-selected series of patients patients with exraglandular symptoms (10/14, (20 women, one man; aged 22-78 years; mean 71%) than in those with only glandular age 53-6) who were admitted to the section of symptoms (29%). Spirometrically 29% (6/21) rheumatology were studied. The diagnosis of of the patients had 'small airways' disease', primary Sjogren's syndrome was based on the and all those had BHR. Of6/21 (29%) who had following findings: each patient had kerato- diffuse interstitial lung disease, two had BHR. conjunctivitis sicca shown by a pathological Three of the four patients with obstructive Schirmer's test (<10 mm/5 min) and positive lung function were challenged with metha- rose bengal staining,7 and xerostomia with a choline and two of them had BHR. Only two total salivary secretion rate stimulated by patients with BHR had normal spirometry chewing of <0 7 ml/min,8 in the absence of findings. The data showed that respiratory other rheumatic diseases. The diagnosis was disease-mostly mild or moderate but even confirmed by a positive lower lip biopsy.9 severe bronchial hyperresponsiveness- is Glandular and extraglandular symptoms of the commonly seen in patients with primary patients were clinically evaluated. All patients Sj6gren's syndrome. underwent serological examinations with the following tests: Waaler-Rose rheumatoid factor http://ard.bmj.com/ and antinuclear antibodies were measured at the Sjogren's syndrome is a chronic autoimmune department of clinical bacteriology, University inflammatory disease, which mainly affects Hospital, Uppsala. Anti-Ro (SS-A) and anti-La exocrine glands. Sjogren's syndrome can occur (SS-B) were measured by the Western blot alone-primary Sjogren's syndrome, or in technique at the State Bacteriological Laboratory association with other autoimmune diseases, in Stockholm, Sweden. such as rheumatoid arthritis, systemic lupus All subjects underwent plain chest radio- on September 25, 2021 by guest. Protected copyright. erythematosus, and systemic sclerosis- graphy and spirometry. The spirometric test secondary Sjogren's syndrome. Several visceral included measurements of the total lung organs, including the lungs,' may be affected in capacity (TLC), residual volume (RV), airways primary Sjogren's syndrome. The respiratory resistance (Raw), and airway conductance manifestations include among others interstitial (Gaw/V) with a body plethysmograph. Vital and Rheumtolgy Section, pneumonitis, 'small airways' disease', capacity (VC), forced vital capacity (FVC), Department of pleuritis.21 Large airway obstruction has been forced expiratory volume in one second (FEVy), Internal Medicine, reported in 8-12% of patients with primary FEVy as a percentage of VC (FEVI/VC) and of Uppsaa University Sjogren's syndrome.5 6In our experience severe TLC (FEV,/TLC), flow volume registrations Hospitl, S-751 85 are to maximal flows Uppala, Sweden obstructive symptoms attributed with exploratory flow Vem.,) and B Gudbj6msson bronchial asthma and the diagnosis of Sjogren's measured at 50%/o (Ve5o) and 25% (Ve25) of FVC R Hiigren syndrome unfortunately does not become were measured with an Ohio spirometer. The Depar met of apparent until the patients develop interstitial slope of the alveolar plateau (phase III), closing Ph lung fibrosis. About one third of patients with volume (CV) as a percentage of VC (CV/VC), UppQla University Hosptl, primary Sjogren's syndrome have a chronic dry and closing capacity (CC) as percentage of TLC Uppsala, Sweden non-productive cough and dyspnoea.2 3 These (CCITLC) were determined with the single H Hedenstr6m symptoms are thought to be due to dryness in breath nitrogen washout test and the transfer Department of the large airways, secondary to a lymphocyte factor of the lung for CO (TLco) was measured Lung Medicine, infiltration of the glands of the mucous mem- with the transfer test. The values obtained were Hospial, Uppsala, brane in the trachea. These so-called xerotrachea compared with those for healthy controls Sweden symptoms may, however, also imitate the matched for age and sex, and abnormal values G Sthienheim symptoms of mild or moderate bronchial hyper- were defined as values outside the 95% con- Correspondence to: us 11 Dr reactivity. This clinical background induced fidence intervals.'0 Gudbj6rnsson. of bronchial The methacholine test was modified from Accepted for publication to investigate the prevalence 1 February 1990 hyperresponsiveness (BHR) to methacholine Hargreave's method.'2 A hand-held deVilbiss Bronchial yperresponsiveness inprina Sjogren's syndrome 37 Tabk I Sex, age, serology, extraglandular mamfestations and respiratory symptoms in 21 patients with primary Sjogren's drome Ann Rheum Dis: first published as 10.1136/ard.50.1.36 on 1 January 1991. Downloaded from Case Sex Age Serolorv Extraglandukir Pulmuny No (years) toms sympom RF* ANA* iiire fire, patern 1 F 22 -t - Sun sensitivity None 2t F 60 1/125 - Raynaud's Dry coughing 3 F 38 1/25 - Raynaud's Dry coughing 4 F 78 1/640 1/100 Raynaud's Exertional dyspnoea Speckled S F 60 - 1/25 BC,* NEAr,* HTh,* Dry coughing Homogeneous Raynaud's 6 F 71 - 1/1600 NEAr, Raynaud's, 'Asthma' Nucleolar kidney stone 7 F 63 - 1/1600 NEAr, Wmgl,* Dry coughing Nucleolar polyneuropathy, kidney stone 8 F 62 - - None Exertional dyspnoea 9t F 55 1/80 1/25 None Dry coughing Homogeneous 10 F 55 - - None None 11 F 40 - 1/400 None None Homogeneous 12tt F 41 1/80 - None 'Asthma' 13 F 63 - - None Exertional dyspnoea 14 F 43 - 1/100 Kidney stone, Dry coughing Homogeneous cutaneous vasculitis 15 F 51 1/25 - Sun sensitivity, Dry coughing Raynaud's 16 F 56 1/25 1/25 HTh, NEAr, None Speckled Raynaud's 17t F 46 - 1/100 Raynaud's Dry coughing Homogeneous 18 F 38 - 1/3200 Kidney stone, Dry coughing Homogeneous non-Hodgkin's lymphoma, leucopenia, neuropathy 19 M 63 - - NEAr, Raynaud's None 20 F 60 - - Raynaud's Exertional dyspnoea 21 F 50 1/160 1/25 None None Speckled 'RF=rheumatoid factor; ANA=antinuclear antibody; BC=biliary cirrhosis; NEAr=non-erosive arthritis; HTh=hypothyroidism; Wmgl=Waldenstr6m's macroglobulinaemia. tSmokers; ttex-smoker. *-indicates a titre <1/25. 646 nebuliser was used. After an initial test with METHACHOLINE CHALLENGE TEST RESULTS saline the patients were tested with double Twenty patients underwent the methacholine http://ard.bmj.com/ dilutions of methacholine, at three minute inhalation challenge test. One patient (case No intervals, starting with 1-2 mg/ml up to a 12) had an FEV1 lower than 1-0 1/min before maximum dose of 20 mg/ml. The subject methacholine inhalation and was therefore not inhaled for two minutes actuating the nebuliser challenged with methacholine. The bronchial during each inhalation. The nebuliser was response to methacholine inhalation showed weighed before and after each inhalation and that 12/20 (60%) of the patients fulfilled the the consumed dose calculated. The inhalation criteria for BHR. One patient had severe BHR, on September 25, 2021 by guest. Protected copyright. was discontinued when there was a fall in the five moderate, four mild, and two patients had FEV1 of 20% or more below the lowest post- slight BHR (table 2). In the reference group saline value. The test result was expressed as the only two subjects had mild BHR (their PD20 provocation dose which caused a fall in FEVy values were 3-2 mg and 3-4 mg). of 20% (PD20). The degree of BHR was divided into categories based on the PD20 value: severe (<0-125 mg methacholine), moderate (0-125- CLINICAL SYMPTOMS AND BRONCHIAL 1-2), mild (1-3-5-0), and slight (5-1-9-0). HYPERRESPONSIVENESS Twenty one healthy subjects (19 women, two Dry non-productive coughing and foreign body men; aged 29-63 years; mean age 48 years) sensation in the pharynx were noted in nine of served as controls. One was a smoker and three the 21 patients. No one had productive cough. were ex-smokers. Exertional dyspnoea was seen in six of the 21 patients; in two of these patients asthma had been diagnosed. They suffered from inter- Results mittent wheezing, chest tightness, and breath- The onset of the Sjogren's disease occurred two lessness. Two patients had a history of pleuritis to 21 years (mean 9-5) before respiratory and five patients had frequent respiratory evaluation. Seven of 21 patients (33%) had only infections. Only four patients had smoked glandular symptoms, whereas extraglandular (table 1). Clinical examination showed that two symptoms as well were evident in 14 patients patients had bilateral basal rales and four (67%) (table 1). Fifteen patients (71%) had patients had prolonged expiration, one of whom positive rheumatoid factor or antinuclear had forced expiratory, low pitched rhonchi. antibody titres, or both (table 1). Only three Seven patients had no extraglandular patients were anti-SSA and anti-SSB positive, symptoms; two of these (29%) had evidence of however (case nos 14, 15, and 18).