INTERNET-BASED HOME MONITORING OF PULMONARY FUNCTION AFTER LUNG TRANSPLANTATION. 2000, 25 patients underwent heart lung (HLT) or bilateral-lung (BLT)

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1 Online Supplement for: INTERNET-BASED HOME MONITORING OF PULMONARY FUNCTION AFTER LUNG TRANSPLANTATION METHODS Patients Between the start of the study in June 1998 and the end of the study in September 2000, 25 patients underwent heart lung (HLT) or bilateral-lung (BLT) transplantation at our center. Of these, 4 patients were excluded from the study because of early complications and death within the first postoperative year, 1 patient was excluded because of his inability to provide reliable functional data, and 1 patient refused to participate. Nineteen patients (8 male) (numbers 1 19) with HLT (n = 7) or BLT (n = 12) were thus included in the home-monitoring program within days after discharge from hospital. We also studied 3 additional patients (numbers 20 22) who had received BLT before June 1998 and were included days after surgery. All 22 patients gave oral informed consent to participation in the program, which had been approved by the Ethic Committee of the institution. Details of the patients are given in Table 1 of the main text. At the time of transplantation, they were aged 18 to 55 years (mean ± SD, 33.5 ± 11.2 years). Preoperative diagnosis was cystic fibrosis in 11 patients, primary pulmonary hypertension in 4 patients, Eisenmenger syndrome in 3 patients, emphysema in 2 patients, bronchiectasis in 1 patient, and lymphangioleiomyomatosis in 1 patient. Induction immunosuppressive therapy consisted of antithymocyte globulin, cyclosporine, azathioprine or mycophenolate mofetyl, and methylprednisolone. Maintenance immunosuppression was based on cyclosporine or tacrolimus, azathioprine or mycophenolate mofetyl, and E1

2 methylprednisolone. Augmented immunosuppression for allograft rejection included increased corticosteroid dosage and/or additional courses of antithymocyte globulin. Study Method The Internet-based system used in this study has been previously described in details (E1). Briefly, it consisted of a PC-based user-friendly terminal with a keypad and a screen, a modem, and a microspirometer (Microloop II; Micro Medical, Rochester, UK) at home and a central server with a database at the hospital. Patients were instructed to perform at least two measurement sessions a day, one in the morning and one in the evening, preferably at the same time of the day to reduce the effect of diurnal variation in lung function (E2); when patients missed more than 2 3 consecutive days of measurements, they were contacted by the nursing team or the transplant physician to discuss measurement and transmission problems. A session consisted of first answering a symptom questionnaire using the computer (temperature on a scale from 36 to 40 C; breathlessness at rest and on exercise on a scale from 0 to 10; increased sputum: yes/no; chest pain: yes/no; increased fatigue: yes/no) and then performing one to three forced expiratory maneuvers. The patients were provided with real-time visual feedback, the current flow volume curve being superimposed on the best personal reference curve; the computer asked the patient to perform up to two additional maneuvers whenever the FEV 1 was below 100% of the reference value. The reference flow volume curve was initially recorded at the transplant center under supervision of the transplant physician; thereafter, it was regularly updated as lung function improved in the postoperative period. The flow volume loop with E2

3 the highest FEV 1 was date and time stamped and was transmitted to the transplant center for further analysis. We selected the maneuver with the highest FEV 1 because previous studies in recipients of heart lung and bilateral-lung grafts have shown that this variable is more sensitive than others (e.g., FVC) to acute infection or rejection (E3). Hospital spirometry was obtained with a Sensormedics 2400 unit (Sensormedics, Anaheim, CA) once a week during the first three postoperative months, twice a month between postoperative Months 4 6, once a month between postoperative Months 7 12, and every two months after the first postoperative year and when clinically indicated. Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBB) was performed on postoperative Months 1, 3, 6, and 12 as part of the surveillance protocol and when clinically indicated. Data Analysis Patient adherence was calculated as the number of days with one or with two measurement sessions divided by the number of days on which the patient was able to perform the measurements (i.e., holidays; days of hospitalization or technical failure were excluded). The agreement between home and hospital measurements obtained on the same day or on two consecutive days was assessed by the method of Bland and Altman (E4). Individual baselines and coefficients of variation (CV) were calculated once a week for forced expiratory volume in 1 s (FEV 1 ) and mid-expiratory flow rate between 25% and 75% of forced vital capacity (FEF ) from data obtained during the previous week (or during the previous two weeks if the number of measurements was below 10), and the individual value for a significant change (VSC) was calculated as the fifth E3

4 percentile of the normal one-tailed distribution by multiplying the CV by 1.65 (E5). The same data were used by the hospital server to recalculate the baseline and cutoff values (baseline minus VSC) for FEV 1 and FEF once a week, which was done to take into account progressive decreases or increases in pulmonary function. Three consecutive measurements of one or both variables showing a decrease from baseline that exceeded the personal VSC generated an alarm at the hospital. Because we asked the patients to measure their spirometry twice daily, three consecutive measurements corresponded to a functional decline persisting for at least one day. Whenever an alarm was generated at the hospital, the transplant physician called the patient to ask questions regarding the patient s health status. Patients who reported new respiratory symptoms or temperature, were asked to come to the hospital on the same or the next day to answer a standardized symptom questionnaire, perform a spirometry, undergo a physical examination and, if appropriate, a fiberoptic bronchoscopy with BAL and TBB, which were used as gold standards. Only findings on BAL/TBB that deserved treatment were considered clinically significant (e.g., acute cellular rejection <A 2 and bacterial colonization were discarded). If there was an obvious explanation for the functional degradation (e.g., a significant bleeding during the TBB procedure performed on the preceding day or a recent rib fracture), BAL/TBB was not performed. Similarly, if the patient did not report a new symptom, home pulmonary function was closely followed, and the patient was contacted to perform additional procedures only if the functional decline persisted for more than one day. The alarm episodes were classified as true positives (alarms that could be accounted for by a precise diagnosis), false positives (alarms for which no precise diagnosis could be found, or functional declines that were not E4

5 accompanied by symptoms and lasted for no more than one day), and false negatives (episodes for which a BAL/TBB yielded a precise diagnosis but did not generate an alarm) and the sensitivity and positive predictive value of home spirometry for the detection of acute allograft dysfunction was computed. The number of true negatives (TN), and hence the specificity, was not calculated because we considered it inappropriate to categorize patients as TN based only on a stable lung function and the absence of symptoms (i.e., without BAL/TBB). Data are expressed as mean ± SD throughout the text and tables. References E1. Morlion B, Verbandt Y, Paiva M, Estenne M, Michils A, Sandron P, Bawin C, Assis-Arantes P. A telemanagement system for home follow-up of respiratory patients: a PC-based home monitoring system for improved management of lung transplant and asthmatic cases. IEEE Eng Med Biol Mag 1999;18: E2. Morrison JF, Higenbottam TW, Hathaway TJ, Clelland C, Scott JP, Wallwork. J. Diurnal variation in FEV 1 after heart-lung transplantation. Eur Respir J 1992;5: E3. Van Muylem A, Melot C, Antoine M, Knoop C, Estenne M. Role of pulmonary function in the detection of allograft dysfunction after heart-lung transplantation. Thorax 1997;52: E4. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1: E5. Pennock BE, Rogers RM, McCaffree DR. Changes in measured spirometric indices: what is significant? Chest 1981;80: E5