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1.  Pulmonary function in Parkinson's disease. 
Pulmonary function was investigated in 31 consecutive patients with relatively severe Parkinson's disease. Clinical disability was assessed by Hoehn and Yahr scale, Northwestern University Disability Scale and Websterscore. All patients were on levodopa substitution therapy and used anticholinergics. Pulmonary function was investigated by spirography, determination of a maximal inspiratory and expiratory flow-volume curve and, when possible, maximal static mouth pressures were determined. Peak inspiratory and expiratory flow, maximal expiratory flow at 50% and maximal static mouth pressures were significantly below normal values. Vital capacity, forced inspiratory volume in 1 s and the ratio of forced expiratory volume in 1 s and vital capacity were relatively normal. Nine patients had upper airway obstruction (UAO) as judged by abnormal values for peak inspiratory flow, the ratio of forced expiratory volume in 1 s and peak expiratory flow and the ratio of maximal expiratory and inspiratory flow at 50%. Flow-volume curves were normal in eight patients; four patients demonstrated flow decelerations and accelerations (type A) and 16 had a rounded off flow-volume curve (type B). Type A can be explained by UAO and type B by a combination of decreased effective muscle strength and possible UAO. Overall results of pulmonary function tests in patients without any clinical signs or symptoms of pulmonary disease point to subclinical upper airway obstruction and decreased effective muscle strength in a significant proportion of patients.
PMCID: PMC1032405  PMID: 2926415
2.  Sleep related upper airway obstruction in a cohort with Down's syndrome. 
Archives of Disease in Childhood  1991;66(11):1333-1338.
The prevalence of sleep related upper airway obstruction (UAO) was studied in a cohort of 34 children with Down's syndrome from a geographically defined area. Thirty two (94%) of the children, ranging in age between 0.1 and 4.9 years (median 1.4), underwent full clinical assessment for UAO including parental questionnaires and overnight tape recordings of chest wall movements and arterial oxygen saturation (SaO2). Compared with controls, children with Down's syndrome had (a) an increased incidence of stridor and chest wall recession during sleep, (b) an increased frequency of a pattern on inspiration indicating increased upper airway resistance, (c) a reduced baseline oxygen saturation (having excluded recordings on four children with potential for right to left intracardiac shunting), and (d) an increased number of episodes with SaO2 less than or equal to 90% despite continued chest wall movements. At their initial assessment seven children (22%) had evidence of UAO. The 18 youngest children (less than or equal to 1.7 years) underwent repeated recordings and clinical assessment until they had all reached 2 years of age. A further three were found to have developed UAO. Sleep related UAO is a common problem in children with Down's syndrome, occurring in 10 of 32 (31%) of this population based sample.
PMCID: PMC1793297  PMID: 1836718
3.  Pediatric upper airway obstruction: Inter-observer variability is the road to perdition. Short title: Inconsistent assessments of stridor amongst pediatric practitioners 
Journal of critical care  2013;28(4):490-497.
To determine the inter-observer variability in the clinical assessment of pediatric upper airway obstruction (UAO). To explore how variability in assessment of UAO may contribute to risk factors and incidence of post-extubation UAO.
Prospective trial in two tertiary care Pediatric intensive care units. Bedside practitioners performed simultaneous, blinded UAO assessments on 112 children after endotracheal extubation.
Agreement amongst RTs, RNs and MDs was poor for cyanosis (kappa (κ) =0.01), and hypoxemia at rest (κ =0.14); and fair for consciousness (κ =0.27), air entry (κ =0.32), hypoxemia with agitation (κ =0.27), and pulsus paradoxus (κ =0.23). When looking at “stridor” and “retractions,” defined using more than 2 grades of severity from the Westley Croup Score, the inter-relater reliability was moderate (κ =0.43 and κ =0.47, respectively). This could be improved marginally by dichotomizing the presence or absence of stridor (κ =0.54) or retractions (κ =0.53). The overall incidence of UAO after extubation (stridor plus retractions) could range from 7–22%, depending on how many providers were required to agree.
Physical findings routinely used for UAO have poor inter-observer reliability amongst bedside providers. This variability may contribute to inconsistent findings regarding incidence, risk factors, and therapies for post-extubation UAO.
PMCID: PMC3644547  PMID: 23337481
Airway Obstruction; Pediatrics; Intensive Care; Intubation; Endotracheal
4.  Chronic Upper Airway Obstruction Induces Abnormal Sleep/Wake Dynamics in Juvenile Rats 
PLoS ONE  2014;9(5):e97111.
Conventional scoring of sleep provides little information about the process of transitioning between vigilance-states. We used the state space technique to explore whether rats with chronic upper airway obstruction (UAO) have abnormal sleep/wake states, faster movements between states, or abnormal transitions between states.
The tracheae of 22-day-old Sprague-Dawley rats were surgically narrowed to increase upper airway resistance with no evidence for frank obstructed apneas or hypopneas; 24-h electroencephalography of sleep/wake recordings of UAO and sham-control animals was analyzed using state space technique. This non-categorical approach allows quantitative and unbiased examination of vigilance-states and state transitions. Measurements were performed 2 weeks post-surgery at baseline and following administration of ritanserin (5-HT2 receptor antagonist) the next day to stimulate sleep.
Measurements and Results
UAO rats spent less time in deep (delta-rich) slow wave sleep (SWS) and near transition zones between states. State transitions from light SWS to wake and vice versa and microarousals were more frequent and rapid in UAO rats, indicating that obstructed animals have more regions where vigilance-states are unstable. Ritanserin consolidated sleep in both groups by decreasing the number of microarousals and trajectories between wake and light SWS, and increasing deep SWS in UAO.
State space technique enables visualization of vigilance-state transitions and velocities that were not evident by traditional scoring methods. This analysis provides new quantitative assessment of abnormal vigilance-state dynamics in UAO in the absence of frank obstructed apneas or hypopneas.
PMCID: PMC4019644  PMID: 24824340
5.  Sleep related upper airway obstruction and hypoxaemia in sickle cell disease. 
Archives of Disease in Childhood  1992;67(7):925-929.
A cohort of 53 patients (age range 1.9-16.5 years) with sickle cell disease (49 homozygous SS and four S beta zero-thalassaemia) was studied for evidence of sleep related upper airway obstruction (UAO). This involved (i) a clinical assessment based on a history of snoring, a score of tonsillar size, and (for 50 patients) overnight multichannel respiratory recordings, and (ii) a blinded analysis of arterial oxygen saturation (SaO2) from the above recordings, and comparison with results from 50 healthy age matched controls of both white (n = 25) and Afro-Caribbean race. There was no difference in the baseline SaO2 values of the white and Afro-Caribbean controls. Eighteen patients with sickle cell disease (36%) were found to have sleep related UAO. The blinded analysis showed that eight patients (16%) had episodic hypoxaemia (SaO2 less than or equal to 80%, a value not observed in controls) and/or low baseline SaO2 values (less than 95.8%, the lowest value seen in the controls). Postoperative assessment was undertaken in 15 patients who underwent adenotonsillectomy. All demonstrated an improvement in symptoms and a reduction or abolition of episodic hypoxaemia. Of the 47 patients assessed when free of UAO (not demonstrated on screening, n = 32, or resolved following surgery, n = 15), seven continued to show baseline hypoxaemia. Sleep related UAO and baseline hypoxaemia are common complications of sickle cell disease in children.
PMCID: PMC1793846  PMID: 1308102
6.  The use of computed tomography in the evaluation of large multinodular goitres. 
This study reports one unit's experience of the value of computed tomography (CT) in the evaluation of 24 patients with large cervical and retrosternal goitres. Of these patients, 17 were thought clinically to have symptoms of tracheal compression, but the CT demonstrated significant narrowing in only 12 cases. In the other five patients, surgery was deferred and other causes for their symptoms sought and treated. Seven patients were asymptomatic and CT failed to reveal any evidence of tracheal compression in six. In the remaining patient, however, CT revealed gross narrowing and urgent surgery was performed. When compared with CT, chest/thoracic inlet radiographs were misleading in 48% of patients, with tracheal narrowing being overestimated and underestimated. We conclude that CT gives useful information about tracheal compression in patients with large multinodular goitres, and is more accurate than chest/thoracic inlet radiographs.
PMCID: PMC2499357  PMID: 1996861
7.  Continuous positive airway pressure and ventilation are more effective with a nasal mask than a full face mask in unconscious subjects: a randomized controlled trial 
Critical Care  2013;17(6):R300.
Upper airway obstruction (UAO) is a major problem in unconscious subjects, making full face mask ventilation difficult. The mechanism of UAO in unconscious subjects shares many similarities with that of obstructive sleep apnea (OSA), especially the hypotonic upper airway seen during rapid eye movement sleep. Continuous positive airway pressure (CPAP) via nasal mask is more effective at maintaining airway patency than a full face mask in patients with OSA. We hypothesized that CPAP via nasal mask and ventilation (nCPAP) would be more effective than full face mask CPAP and ventilation (FmCPAP) for unconscious subjects, and we tested our hypothesis during induction of general anesthesia for elective surgery.
In total, 73 adult subjects requiring general anesthesia were randomly assigned to one of four groups: nCPAP P0, nCPAP P5, FmCPAP P0, and FmCPAP P5, where P0 and P5 represent positive end-expiratory pressure (PEEP) 0 and 5 cm H2O applied prior to induction. After apnea, ventilation was initiated with pressure control ventilation at a peak inspiratory pressure over PEEP (PIP/PEEP) of 20/0, then 20/5, and finally 20/10 cm H2O, each applied for 1 min. At each pressure setting, expired tidal volume (Vte) was calculated by using a plethysmograph device.
The rate of effective tidal volume (Vte > estimated anatomical dead space) was higher (87.9% vs. 21.9%; P<0.01) and the median Vte was larger (6.9 vs. 0 mL/kg; P<0.01) with nCPAP than with FmCPAP. Application of CPAP prior to induction of general anesthesia did not affect Vte in either approach (nCPAP pre- vs. post-; 7.9 vs. 5.8 mL/kg, P = 0.07) (FmCPAP pre- vs. post-; 0 vs. 0 mL/kg, P = 0.11).
nCPAP produced more effective tidal volume than FmCPAP in unconscious subjects.
Trial registration identifier: NCT01524614.
PMCID: PMC4056076  PMID: 24365207
8.  Extent of Subclinical Pulmonary Involvement in Childhood Onset Systemic Lupus Erythematosus in the Sultanate of Oman 
Oman Medical Journal  2012;27(1):36-39.
The aim of this study was to investigate the frequency of pulmonary function abnormalities in clinically asymptomatic children with Systemic Lupus Erythematosus and to determine the relationship of these abnormalities to clinical, laboratory, and immunological parameters as well as to disease activity.
Forty-two children with childhood onset Systemic Lupus Erythematosus were included in this study. Demographic, clinical, laboratory and immunological parameters, as well as disease activity were assessed. Pulmonary function tests (PFT) were performed routinely to screen for subclinical lung disease.
Out of the 42 children, 19% (n=8) had clinical evidence of pulmonary involvement. The patients with no clinical evidence of pulmonary involvement (n=34) represent the study cohort. From our cohort of patients with no clinical evidence of pulmonary involvement 79% (n=27) had PFT abnormality; including 62% (n=21) had reduced FVC, 71% (n=24) had reduced FEV1, and 67% (n=12) had reduced DLCO. Similarly, 56% (n=15) had a restrictive PFT pattern, and 2.6% (n=2) had an obstructive PFT pattern, while 33% (n=7) had an isolated impairment of diffusion capacity. Due to small sample size; it was not possible to find a statistically significant difference between the cohort of asymptomatic SLE patients with abnormal PFT findings (n=27) and those with normal PFT findings (n=7) in terms of clinical, laboratory, immunological or disease activity index score.
Subclinical lung disease, as demonstrated by abnormal PFT in patients with normal radiographs, may be common but should be interpreted with caution as an early sign of lung disease. Although PFT studies do not correlate well with pulmonary symptoms in patients with childhood onset SLE, they nevertheless provide objective quantification of the type and severity of the functional lesions.
PMCID: PMC3282137  PMID: 22359723
Systemic lupus erythematosus; Pulmonary; Prevalence; Oman
9.  Continuous positive airway pressure titration in infants with severe upper airway obstruction or bronchopulmonary dysplasia 
Critical Care  2013;17(4):R167.
Noninvasive continuous positive airway pressure (CPAP) is recognized as an effective treatment for severe airway obstruction in young children. The aim of the present study was to compare a clinical setting with a physiological setting of noninvasive CPAP in infants with nocturnal alveolar hypoventilation due to severe upper airway obstruction (UAO) or bronchopulmonary dysplasia (BPD).
The breathing pattern and respiratory muscle output of all consecutive infants due to start CPAP in our noninvasive ventilation unit were retrospectively analysed. CPAP set on clinical noninvasive parameters (clinical CPAP) was compared to CPAP set on the normalization or the maximal reduction of the oesophageal pressure (Poes) and transdiaphragmatic pressure (Pdi) swings (physiological CPAP). Expiratory gastric pressure (Pgas) swing was measured.
The data of 12 infants (mean age 10 ± 8 mo) with UAO (n = 7) or BPD (n = 5) were gathered. The mean clinical CPAP (8 ± 2 cmH2O) was associated with a significant decrease in Poes and Pdi swings. Indeed, Poes swing decreased from 31 ± 15 cmH2O during spontaneous breathing to 21 ± 10 cmH2O during CPAP (P < 0.05). The mean physiological CPAP level was 2 ± 2 cmH2O higher than the mean clinical CPAP level and was associated with a significantly greater improvement in all indices of respiratory effort (Poes swing 11 ± 5 cm H2O; P < 0.05 compared to clinical CPAP). Expiratory abdominal activity was present during the clinical CPAP and decreased during physiological CPAP.
A physiological setting of noninvasive CPAP, based on the recording of Poes and Pgas, is superior to a clinical setting, based on clinical noninvasive parameters. Expiratory abdominal activity was present during spontaneous breathing and decreased in the physiological CPAP setting.
PMCID: PMC4056687  PMID: 23889768
Airway obstruction; Continuous positive airway pressure; Oesophageal pressure; Expiratory abdominal activity; Infant
10.  Negative Pressure Pulmonary Edema After Oral and Maxillofacial Surgery 
Anesthesia Progress  2009;56(2):49-52.
Negative pressure pulmonary edema (NPPE) following upper airway obstruction (UAO) has been reported in several clinical situations. The main cause of NPPE is reported to be increased negative intrathoracic pressure. We present a case of NPPE that occurred after general anesthesia for plate removal after jaw deformity surgery. After completion of the surgery, administration of inhaled anesthetics was stopped and the patient opened his eyes on verbal command. Immediately after extubation, the patient stopped breathing and became cyanotic. Acute UAO following laryngospasm was suspected. Soon after reintubation, pink, frothy fluid came out of the endotracheal tube, and a tentative diagnosis of NPPE was made. Continuous positive airway pressure was applied. In addition, furosemide and dexamethasone were administered. By the next day, the symptoms had almost disappeared.
PMCID: PMC2699692  PMID: 19642719
Negative pressure pulmonary edema; Upper airway obstruction; Continuous positive airway pressure
11.  Corticosteroids to prevent postextubation upper airway obstruction: the evidence mounts 
Critical Care  2007;11(4):156.
Intubation of the airway can lead to laryngotracheal injury, resulting in extubation failure from upper airway obstruction (UAO). A number of factors can help to identify patients who are at greatest risk for postextubation UAO. Three randomized controlled trials demonstrate that prophylactic corticosteroids decrease the risk for postextubation UAO and probably the need for re-intubation.
PMCID: PMC2206510  PMID: 17705879
12.  A Case of Airway Obstruction Secondary to Acute Haemorrhage into a Benign Thyroid Cyst 
Case Reports in Critical Care  2014;2014:372369.
A 70-year-old female, with a history of progressive dyspnoea, was admitted to the critical care unit after successful resuscitation following a witnessed, out of hospital cardiorespiratory arrest. A presumptive diagnosis of cardiorespiratory arrest secondary to an exacerbation of chronic obstructive pulmonary disease was made. However, on more detailed examination a large anterior, midline neck mass was noted. Following tracheal intubation, a computerised tomography scan of the patient's neck and thorax revealed a seven-centimetre, well-defined, nonenhancing, rounded homogeneous opacity at the thoracic inlet, consistent with a large midline thyroid cyst. Needle aspiration of the cyst was performed and yielded approximately 50 mL of frank blood. After an uncomplicated tracheal extubation and recovery, an elective subtotal thyroidectomy was performed prior to hospital discharge. Histology of the specimen revealed a benign thyroid cyst within a multinodular goitre. Euthyroid multinodular goitres are more likely to be managed conservatively due to an asymptomatic clinical course in most patients. However, the risk of respiratory distress and acute airway obstruction from tracheal compression or acute haemorrhage should be kept in mind. Patients at risk of this life threatening complication should be managed with elective thyroidectomy to reduce morbidity and mortality.
PMCID: PMC4158169  PMID: 25215246
13.  A rare instance of retrosternal goitre presenting with obstructive sleep apnoea in a middle-aged person 
In endemic goitre areas, 20% of the population over 70 will have retrosternal goitre.12 Obstructive sleep apnoea (OSA) occurs when there are repeated episodes of complete or partial blockage of the upper airway during sleep.
A 55-year-old man was being treated for obstructive sleep apnoea, came with stridor worsening over the 2 and was advised CPAP ventilation. In our institution, he was diagnosed to have goitre with retrosternal extension with no hypo/hyperthyroidism. He was an obese (BMI – 30 Kg/m2) male with a short, broad neck and clinically no obvious swelling in the neck. He had stridor, with positive Kocher's test as well as Pemberton's sign. His TFT's were normal and CT scan revealed widening of superior mediastinum. Patient was pre-medicated with low dose (0.1 μg) fentanyl, and induced with inhalational anaesthesia (sevoflourane). Endotracheal intubation was done using 6 no. ET tube, without muscle relaxation, and the thyroid was removed through a conventional Kocher's incision. Thyroid was enlarged 25 cm by 10 cm in retrosternal position. Postoperatively, pt was reversed and shifted to ICU, was monitored for the next 24 hours. He was extubated uneventfully the next morning. Patient had a good post-op recovery and was discharged on the 7th post-op day.
Terms such as retrosternal, substernal, intrathoracic, or mediastinal have been used to describe a goitre that extends beyond the thoracic inlet. However, there is a lack of consensus regarding the exact definition of a retrosternal goitre (RSG).1 The majority of patients present with shortness of breath or asthma like symptoms (68.8%), as was the case in the studied patient. Other modes of presentation include neck mass (75%), hoarseness of voice (37.5%), dysphagia (31.3%), stridor/wheezing (19%), or SVC obstruction. Upper airway obstruction due to thyroid gland has been reported up to 31%2 and difficulty in intubation has been reported in 11%.3 Central airway obstruction produces symptoms of dyspnoea, stridor, or obstructive pneumonia and is often misdiagnosed as asthma.4 The CT scan was the most useful tool showing the nature and extent of the lesion in the reported case. In a recent publication, the CT scan was considered the gold-standard preoperative radiological investigation.5 Surgery is the only effective treatment for retrosternal goitres. In most cases, suppressive therapy with thyroxine is ineffective in reducing the size of multinodular goitres;7,8 radio-iodine therapy is both generally ineffective in large goitres8 and may induce acute inflammation and swelling of the gland with the potential for airway obstruction. The operation of choice is usually a total thyroidectomy. Only around 2% of patients undergoing thyroidectomy for retrosternal goitre will require surgical access other than a standard collar incision (either manubriotomy, sternotomy or thoracotomy).9
Despite all the advances in investigative modalities, retrosternal goitre still exists in 20% of patients over 70 years in endemic regions. It has to be recognised that it can be a cause of obstructive sleep apnoea. Early detection and prompt management goes a long way in decreasing the morbidity and mortality in patients with RSG.
PMCID: PMC3860032  PMID: 24212758
Retrosternal goitre; Obstructive sleep apnoea
14.  A Multi Detector Computed Tomography Survey of Tracheal Diverticulum 
The Eurasian Journal of Medicine  2013;45(3):145-148.
Tracheal diverticulum (DV) is an incidental finding in thoracic computed tomography examinations. Tracheal DV may be associated with chronic cough and chronic obstructive pulmonary disease (COPD). A few studies have investigated the relationship between tracheal DV and COPD. There is still no consensus on the relationship. The purpose of this study was to determine the incidence of tracheal DV and its coexistence with bronchial DV and hyperaeration.
Materials and Methods:
For the study, 299 patients from a total number of 12 800 patients who underwent a thoracic computed tomography examination were included. Tracheal diverticula were evaluated for localization, size, contour, wall thickness and communication with the tracheal lumen. The association of tracheal DV with bronchial DV and hyperaeration was also noted. The relationship between tracheal DV and hyperaeration was analyzed.
Of the 299 patients, a total of 412 tracheal diverticula were observed. Out of these, 148 of the tracheal diverticula were in females, and 264 of the tracheal diverticula were in male patients. The incidence of tracheal DV was determined to be 2.38% in this study. In total, 400 of the tracheal diverticula (97.1%) were located at the right posterolateral aspect of the trachea, and 320 of the tracheal diverticula were associated with hyperaeration. There was no significant relation between the tracheal DV and hyperaeration. However, 84 of 412 tracheal diverticula had a bronchial DV, and 72 of 84 of these bronchial DV were associated with COPD. Statistical analysis indicated a significant correlation with COPD and bronchial DV (p<0.05).
Tracheal DV is often asymptomatic and mostly located in the right posterolateral aspect of the trachea. Tracheal DV is more common in men than in women. The incidence of tracheal DV was 2.38% in this study. Our data demonstrate that there was no significant association between tracheal DV and COPD. However, there was a significant association between subcarinal bronchial DV and COPD.
PMCID: PMC4261431  PMID: 25610271
Bronchi; Chronic Obstructive Pulmonary Disease; computed tomography; diverticula; trachea
15.  Lobar analysis of collapsibility indices to assess functional lung volumes in COPD patients 
We investigated correlations between lung volume collapsibility indices and pulmonary function test (PFT) results and assessed lobar differences in chronic obstructive pulmonary disease (COPD) patients, using paired inspiratory and expiratory three dimensional (3D) computed tomography (CT) images.
We retrospectively assessed 28 COPD patients who underwent paired inspiratory and expiratory CT and PFT exams on the same day. A computer-aided diagnostic system calculated total lobar volume and emphysematous lobar volume (ELV). Normal lobar volume (NLV) was determined by subtracting ELV from total lobar volume, both for inspiratory phase (NLVI) and for expiratory phase (NLVE). We also determined lobar collapsibility indices: NLV collapsibility ratio (NLVCR) (%) = (1 − NLVE/NLVI) × 100%. Associations between lobar volumes and PFT results, and collapsibility indices and PFT results were determined by Pearson correlation analysis.
NLVCR values were significantly correlated with PFT results. Forced expiratory volume in 1 second, measured as percent of predicted results (FEV1%P) was significantly correlated with NLVCR values for the lower lobes (P<0.01), whereas this correlation was not significant for the upper lobes (P=0.05). FEV1%P results were also moderately correlated with inspiratory, expiratory ELV (ELVI,E) for the lower lobes (P<0.05). In contrast, the ratio of the diffusion capacity for carbon monoxide to alveolar gas volume, measured as percent of predicted (DLCO/VA%P) results were strongly correlated with ELVI for the upper lobes (P<0.001), whereas this correlation with NLVCR values was weaker for upper lobes (P<0.01) and was not significant for the lower lobes (P=0.26).
FEV1%P results were correlated with NLV collapsibility indices for lower lobes, whereas DLCO/VA%P results were correlated with NLV collapsibility indices and ELV for upper lobes. Thus, evaluating lobar NLV collapsibility might be useful for estimating pulmonary function in COPD patients.
PMCID: PMC4266257  PMID: 25525352
segmentation; emphysema; computed tomography; pulmonary function
16.  Unilateral thyroidectomy for the treatment of benign multinodular goiter 
The Journal of surgical research  2013;184(1):514-518.
Benign multinodular goiter (MNG) is one of the most commonly treated thyroid disorders. While bilateral resection is the accepted surgical treatment for bilateral MNG, the appropriate surgical resection for unilateral MNG continues to be debated. Bilateral resection generally has lower recurrence rates but higher complication rates than unilateral resection. Therefore, the purpose of this study was to define the recurrence and complication rates of unilateral and bilateral resections in order to determine the appropriate intervention for patients with unilateral, benign MNG.
We reviewed a prospectively maintained database of all patients who underwent a thyroidectomy for treatment of benign MNG at a single institution between May 1994 and December 2011. All patients with bilateral MNG were treated with bilateral resection. Surgical treatment for unilateral MNG was determined by surgeon preference, with all but one surgeon opting for unilateral resection to treat unilateral MNG. Data were reported as means ± standard error of the mean. Chi-squared analysis was used to determine statistical significance at a level of p<0.05.
A total of 683 patients underwent thyroidectomy for MNG. Of these patients, 420 (61%) underwent unilateral resection and 263 patients (39%) underwent total thyroidectomy. The mean age was 52±17 years, and 542 patients (79%) were female. The mean follow-up time was 46.1±1.9 months. The rate of recurrent disease was similar between unilateral (2%, n=10) and bilateral (1%, n=3) resections (p=0.248). Unilateral resection patients had a lower total complication rate than patients with bilateral resections (8% vs. 26%, p<0.001); however, there was no difference in the rate of permanent complications (0.2% vs. 1%, p=0.133). Thyroid hormone replacement was rare in unilateral resection patients, but necessary in all patients with bilateral resection (19% vs. 100%, p<0.001).
Patients that had unilateral resections endured less overall morbidities than those who had bilateral resections, and their risk of recurrent disease was similar. They were also significantly less likely to require lifelong hormone replacement therapy post-operatively. Although bilateral resection remains the recommended treatment for bilateral MNG, this data strongly supports the use of unilateral thyroidectomy for the treatment of unilateral, benign MNG.
PMCID: PMC3759563  PMID: 23688788
thyroidectomy; lobectomy; multinodular; goiter; MNG; resection; thyroid; complications; recurrence; levothyroxine
17.  Assessment of Lung Volume Collapsibility in Chronic Obstructive Lung Disease Patients Using CT 
European radiology  2013;23(6):1564-1572.
To investigate the collapsibility of the lung and individual lobes in patients with COPD during inspiration/expiration and assess the association of whole lung and lobar volume changes with pulmonary function tests (PFTs) and disease severity.
PFT measures used were RV/TLC%, FEV1% predicted, FVC, FEV1/FVC%, DLco% predicted and GOLD category. A total of 360 paired inspiratory and expiratory CT examinations acquired in 180 subjects were analysed. Automated computerised algorithms were used to compute individual lobe and total lung volumes. Lung volume collapsibility was assessed quantitatively using the simple difference between CT computed inspiration (I) and expiration (E) volumes (I-E), and a relative measure of volume changes, (I-E)/I.
Mean absolute collapsibility (I-E) decreased in all lung lobes with increasing disease severity defined by GOLD classification. Relative collapsibility (I-E)/I showed a similar trend. Upper lobes had lower volume collapsibility across all GOLD categories and lower lobes collectively had the largest volume collapsibility. Whole lung and left lower lobe collapsibility measures tended to have the highest correlations with PFT measures. Collapsibility of lung lobes and whole lung were also negatively correlated with the degree of air trapping between expiration and inspiration, as measured by mean lung density. All measured associations were statistically significant (P < 0.01).
Severity of COPD appears associated with increased collapsibility in the upper lobes, but change (decline) in collapsibility is faster in the lower lobes.
PMCID: PMC3657332  PMID: 23494492
lung volume; collapsibility; COPD; computed tomography; disease severity
18.  Malignancy rate in nondominant nodules in patients with multinodular goiter: Experience with 1,606 cases evaluated by ultrasound-guided fine needle aspiration cytology 
CytoJournal  2011;8:19.
Conventional medical sources recommend the use of fine needle aspiration cytology (FNAC) for single thyroid nodules and the dominant nodule in multinodular goiter (MNG). The purpose of the present study was to analyze the utility of FNAC for multiple thyroid nodules in patients with MNG and to determine the rate of malignancy in teh nondominant nodules.
Materials and Methods:
Our private practice performed ultrasound-guided FNAC on 1,606 patients between February 2001 and February 1, 2010. In the MNG cases, samples were taken from the dominant nodule and from trhee suspicious / nonsuspicious nodules larger than 1 cm on ultrasound. Ninety-four cases were diagnosed as ‘suspiciously malignant’(SUS) or ‘malignant’ (POS) based on FNAC.
The rate of an SUS / POS diagnosis was 5.7% in the dominant nodules; 2.3% of the nondominant nodules had a SUS / POS diagnosis in FNAC (p = 0.0003). Follow-up revealed malignancy in 15 (35.7%) nondominant nodules and in 27 (64.2%) dominant nodules, with 42 MNG cases undergoing surgery. X test showed a ‘p-level of 0.0003’ between the percentages of SUS / POS diagnosis in dominanat and nondominanat nodules. It was less than the significance level of 0.05. Therefore, the result was regarded to be statistically significant.
Nondominant nodules could harbor malignancy. The risk of malignancy in nondominant nodules in MNG should not be underestimated. We have shown that the dominant nodule in patients with MNG was in fact about 2.5 times more likely to be malignant than a nondominant nodule. The use of FNAC for nondominant nodules could enhance the likelihood of detecting malignancy in an MNG.
PMCID: PMC3221080  PMID: 22114619
Fine needle aspiration cytology; malignancy; multinodular goiter nondominant nodules; thyroid
19.  Respiratory symptoms and disease characteristics as predictors of pulmonary function abnormalities in patients with rheumatoid arthritis: an observational cohort study 
Arthritis Research & Therapy  2010;12(3):R104.
Lung involvement is a common extra-articular manifestation of rheumatoid arthritis (RA) that confers significant morbidity and mortality. The objective of the present study is to assess which respiratory symptoms and patient and disease characteristics are most highly associated with pulmonary function test (PFT) abnormalities in an RA patient cohort without clinical cardiovascular disease.
A total of 159 individuals with RA and without clinically evident cardiovascular disease were evaluated. Respiratory symptoms were assessed with the Lung Tissue Research Consortium questionnaire and all patients underwent evaluation with PFTs. Demographic, lifestyle, RA disease and treatment characteristics were collected. Subclinical coronary artery disease was assessed by cardiac computed tomography. Multivariable regression analysis was used to identify pulmonary symptoms and nonpulmonary parameters associated with PFT abnormalities. Areas under the receiver operating characteristic curves (AUC) were calculated to evaluate the discrimination of these variables for identifying patients with PFT abnormalities.
Respiratory symptoms were reported by 42% of the patient population. Although only 6% carried a prior diagnosis of lung disease, PFT abnormalities were identified in 28% of the subjects. Symptoms combined with other patient and RA characteristics (body mass index, current smoking, anti-cyclic citrullinated peptide antibodies, and current prednisone use) performed satisfactorily in predicting the PFT abnormalities of obstruction (AUC = 0.91, 95% confidence interval = 0.78 to 0.98), restriction (AUC = 0.79, 95% confidence interval = 0.75 to 0.93) and impaired diffusion (AUC = 0.85, 95% confidence interval = 0.59 to 0.92). Co-morbid subclinical coronary artery disease did not modify these relationships.
Assessment of respiratory symptoms along with a limited number of clinical parameters may serve as a useful and inexpensive clinical tool for identifying RA patients in need of further pulmonary investigation.
PMCID: PMC2911894  PMID: 20507627
20.  Pulmonary function derangements in isolated or predominant mitral stenosis – Preoperative evaluation with clinico-hemodynamic correlation 
It is well known that mitral stenosis (MS) is complicated by pulmonary hypertension (PH) of varying degrees. The hemodynamic derangement is associated with structural changes in the pulmonary vessels and parenchyma and also functional derangements. This article analyzes the pulmonary function derangements in 25 patients with isolated/predominant mitral stenosis of varying severity.
The aim of the study was to correlate the pulmonary function test (PFT) derangements (done by simple methods) with: a) patient demographics and clinical profile, b) severity of the mitral stenosis, and c) severity of pulmonary artery hypertension (PAH) and d) to evaluate its significance in preoperative assessment.
Subjects and Methods
This cross-sectional study was conducted in 25 patients with mitral stenosis who were selected for mitral valve (MV) surgery. The patients were evaluated for clinical class, echocardiographic severity of mitral stenosis and pulmonary hypertension, and with simple methods of assessment of pulmonary function with spirometry and blood gas analysis. The diagnosis and classification were made on standardized criteria. The associations and correlations of parameters, and the difference in groups of severity were analyzed statistically with Statistical Package for Social Sciences (SPSS), using nonparametric measures.
The spirometric parameters showed significant correlation with increasing New York Heart Association (NYHA) functional class (FC): forced vital capacity (FVC, r = −0.4*, p = 0.04), forced expiratory volume in one second (FEV1, r = −0.5*, p = 0.01), FEV1/FVC (r = −0.44*, p = 0.02), and with pulmonary venous congestion (PVC): FVC (r = −0.41*, p = 0.04) and FEV1 (r = −0.41*, p = 0.04). Cardiothoracic ratio (CTR) correlated only with FEV1 (r = −0.461*, p = 0.02) and peripheral saturation of oxygen (SPO2, r = −0.401*, p = 0.04). There was no linear correlation to duration of symptoms, mitral valve orifice area, or pulmonary hypertension, except for MV gradient with PCO2 (r = 0.594**, p = 0.002). The decreased oxygenation status correlated significantly with FC, CTR, PVC, and with deranged spirometry (r = 0.495*, p = 0.02).
PFT derangements are seen in all grades of severity of MS and correlate well with the functional class, though no significant linear correlation with grades of severity of stenosis or pulmonary hypertension. Even the early or mild derangements in pulmonary function such as small airway obstruction in the less severe cases of normal or mild PH can be detected by simple and inexpensive methods when the conventional parameters are normal. The supplementary data from baseline arterial blood gas analysis is informative and relevant. This reclassified pulmonary function status might be prognostically predictive.
PMCID: PMC4047508  PMID: 24936309
mitral stenosis; pulmonary function test; pulmonary hypertension
21.  Asymptomatic Preclinical Rheumatoid Arthritis-Associated Interstitial Lung Disease 
Objective. Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA) and a significant cause of morbidity and mortality. The objective of this study was to define high-resolution chest CT (HRCT) and pulmonary function test (PFT) abnormalities capable of identifying asymptomatic, preclinical forms of RA-ILD that may represent precursors to more severe fibrotic lung disease. Methods. We analyzed chest HRCTs in consecutively enrolled RA patients and subsequently classified these individuals as RA-ILD or RA-no ILD based on the presence/absence of ground glass opacification, septal thickening, reticulation, traction bronchiectasis, and/or honeycombing. Coexisting PFT abnormalities (reductions in percent predicted FEV1, FVC, TLC, and/or DLCO) were also used to further characterize occult respiratory defects. Results. 61% (63/103) of RA patients were classified as RA-ILD based on HRCT and PFT abnormalities, while 39% (40/103) were designated as RA-no ILD. 57/63 RA-ILD patients lacked symptoms of significant dyspnea or cough at the time of HRCT and PFT assessment. Compared with RA-no ILD, RA-ILD patients were older and had longer disease duration, higher articular disease activity, and more significant PFT abnormalities. Conclusion. HRCT represents an effective tool to detect occult/asymptomatic ILD that is highly prevalent in our unselected, university-based cohort of RA patients.
PMCID: PMC3747456  PMID: 23983768
22.  The Effect of Pulse Methylprednisolone Plus Theophylline Treatment on Clinical, Pulmonary and Inflammatory Markers in Relapses of Multiple Sclerosis 
Balkan medical journal  2013;30(1):33-36.
The aim of this study was to evaluate whether there was a relationship between severity of multiple sclerosis (MS) exacerbation and pulmonary function test (PFT) and to determine the effect of theophylline, which was added to intravenous methylprednisolone, on serum Tumor Necrosis Factor (TNF)-alpha levels and clinical scores in MS relapses.
Study Design:
Double blind randomized controlled trial.
Material and Methods:
The baseline Expanded Disability Status Scale (EDSS) score was determined, PFT was performed and blood was taken for analysis of TNF- alpha in patients with MS exacerbation. Patients were randomly divided into two groups; group 1 received intravenous methylprednisolone+IV theophylline and group 2 intravenous methylprednisolone+placebo for 5 days. PFT and EDSS score were repeated and blood was taken for TNF-alpha on the 5th and 30th days of the treatment.
Twenty-four patients (14 female, 10 male) were included in the study. Mean age was 32.6±9, duration of disease was 5.4±4.2 years, number of exacerbations was 5±2. There was a significant correlation between the number of exacerbations and EDSS score (p=0.000, r=1). Restrictive PFT findings were detected in 8 and decrease in carbon monoxide diffusing capacity (DLCO) in 3 cases. In within-group analysis, EDSS score was found to be decreased on day 5 and still low on day 30 in the theophylline group (baseline 3±1.3; 5th day 2.4±1.6; 30th day 2±1.7). There was no statistically significant difference in the EDSS score of the placebo group (3±1.6; 2.8±1.7; 2.4±1.9 respectively). While serum TNF-alpha level was not changed in the placebo group, there was a non-significant decrease on day 5 and increase on day 30 in the theophylline group. There was no correlation between the clinical parameters, PFT and TNF-alpha level.
There was no correlation between severity of MS and PFT findings. It is suggested that theophylline might be effective in MS exacerbations since it caused decreases in clinical scores; studies with longer treatment duration are needed to clarify its possible anti-inflammatory effect.
PMCID: PMC4116016  PMID: 25207066
Multiple sclerosis; inflammation; theophylline; TNF-alpha
23.  Identification of a KEAP1 Germline Mutation in a Family with Multinodular Goitre 
PLoS ONE  2013;8(5):e65141.
The familial clustering of multinodular goitres (MNGs) with a dominant mode of inheritance has been repeatedly reported. Linkage studies have revealed several genetic loci responsible for familial MNG; however, most of the causative variants remain unknown.
Methods and Results
Through linkage analysis using single-nucleotide polymorphism markers, we identified a new MNG locus on 19p13.2-q12 in a five-generation Japanese MNG family. Subsequent mutation searches focusing on the candidate 25-Mb region of chromosome 19 identified a heterozygous mutation, c.879_880delinsA, p.Asp294Thr, fs*23, in exon 3 of the KEAP1, which plays a central role in the cytoprotection pathway against oxidative stress. Reverse transcriptase-PCR analysis showed low expression of wild type KEAP1 accompanied by no transcription product of mutant allele in the normal and goitre region of thyroid tissues obtained from the proband. In agreement with previous studies showing that KEAP1 negatively regulates NFE2L2, the NFE2L2 target genes GSTA4 and GCLC were up-regulated in the thyroid tissues of the patient.
This study identified the first KEAP1 mutation in MNG. The results provide insights into the pathogenesis of goitre which develops in the organ continuously exposed to oxidative stress during hormone synthesis.
PMCID: PMC3665763  PMID: 23724128
24.  Pulmonary Function after Whole Lung Irradiation in Pediatric Patients with Solid Malignancies 
Cancer  2011;118(5):1450-1456.
Although whole lung irradiation (WLI) is used to treat pulmonary metastases of pediatric solid malignancies, few studies have addressed its long-term pulmonary consequences.
We conducted a retrospective study of longitudinal changes in 171 pulmonary function tests (PFTs) and their relationship with clinical features in 48 survivors of pediatric malignant solid tumors treated with WLI.
Although active respiratory symptoms were seen in only 9 (18.8%) patients, abnormalities in forced vital capacity (FVC; 58.3%), forced expiratory volume in 1 second (FEV1; 64.6%), total lung capacity (TLC; 72.9%), and diffusion capacity of carbon monoxide corrected for hemoglobin (DLCOcorr; 70.8%) were common. At a median follow-up of 9.7 years after WLI, FVC, FEV1, and TLC significantly declined longitudinally (P = .04, .03, and .02, respectively). Focal pulmonary boost irradiation was significantly associated with abnormal FEV1/FVC (P = .03), forced expiratory flow between 25% and 75% forced vital capacity (FEF25%–75%; P = .005), residual volume (RV; P = .005), and RV/TLC (P = .002). Ten patients had baseline PFTs, and FVC, FEV1, TLC and DLCOcorr worsened immediately after radiation, followed by transient improvement but subsequent decline. Thirteen of 32 (40.6%) patients over the age of 18 were smokers.
Pulmonary dysfunction, especially in lung volumes, was prevalent after WLI and worsened over time although most patients were asymptomatic. Boost irradiation impaired pulmonary function, and a significant proportion of patients were smokers. Further studies are planned to assess the predictors and clinical consequences of progressive PFT abnormalities and to evaluate educational interventions.
PMCID: PMC3233655  PMID: 21800284
pulmonary function tests; solid tumor; whole lung irradiation; pediatric cancer; follow-up
25.  Cervical Decompression and Unexpected Soft Tissue Oedema: Case Report 
Acute upper airway obstruction (UAO) is a life threatening complication that is well recognized after carotid endarterectomy, thyroidectomy and pharyngeal area intervention. It is not widely acknowledged that airway obstruction can occur after cervical spinal fusion surgery which was first described in 1955. There are a number of common postoperative problems which may become apparent in the short to medium term. These include: sore throat, dysphagia, hoarseness, dysphonia, recurrent laryngeal nerve palsy and soft tissue swelling.
PMCID: PMC3821119  PMID: 24223347
Airway Obstruction; Endarterectomy, Carotid; Spinal Fusion

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