Pulmonary dysfunction in thalassaemia major: is there any relationship with body iron stores?

Although pulmonary function abnormalities in thalassaemia major (TM) were described in 1980, the pathogenetic mechanism is not clear and data are contradictory, probably because of study heterogeneity and the multifactorial nature of the pathogenesis. We retrospectively analysed 73 adult TM patients to evaluate the prevalence of pulmonary dysfunction in adult TM and investigate relationships with iron load. All patients underwent body plethysmography and carbon monoxide diffusion (DLCO) was assessed in 63, in addition to blood tests, echocardiogram and T2* myocardial and liver magnetic resonance imaging. Restrictive lung disease was present in 26 (35·6%) patients. Serum ferritin levels were higher in patients with restrictive pattern (1526 µg/l vs. 975 µg/l, P = 0·05). Restrictive lung disease did not correlate with cardiac or liver iron overload. However, considering only patients with serum ferritin >2500 µg/l, those with restrictive pattern also had heart (T2* 14·28 ± 9·99 ms vs. 31·59 ± 7·43 ms) and liver iron overload (LIC 16·02 ± 8·44 mg vs. 5·02 ± 2·69 mg Fe/g dry weight) compared to those without restrictive pattern. Twenty-five patients (39·7%) had decreased DLCO. No correlation was observed with iron parameters. In our data restrictive pattern was predominant; we observed a relationship with serum ferritin levels suggesting that iron, particularly its chronic effect, could play a role in the pathogenesis of pulmonary disease.

Body plethysmographic study of specific airway resistance in a sample of healthy adults.

BACKGROUND AND OBJECTIVE: sRaw (specific airway resistance) is a corrected index (Raw multiplied by thoracic gas volume) that describes airway behaviour regardless of lung volume. Normal values of sRaw in adult subjects have never been formally defined. To establish sRaw interpretation criteria and to define a range of reference values, we evaluated variability, reproducibility and reliability of sRaw measurements in a group of healthy adults. METHODS: We analysed 517 subjects of both genders, aged 18-65 (group A), and to assess the reproducibility of the measurements, we investigated intra-individual variation and potential daily and weekly sRaw rhythms in a subgroup of 18 co-operative healthy subjects (group B). RESULTS: In group A, there was no pattern of association between any of the considered anthropometric parameters; mean sRaw was higher in men (6.24 vs.5.95 cmH2O s in females; P = 0.0128), but when the data were stratified by age, gender-related differences were only found in the group aged 46-60 (males 6.45 cmH2O s, females 6.01 cmH2O s; P = 0.0219). In group B, there was no statistically significant, time-dependent variation during the single tests, nor any circadian or weekly rhythm. CONCLUSIONS: sRaw is a reliable parameter; therefore, we propose that the lower and upper 95% confidence limits should be considered as reference values for adults of both genders, regardless of age. The availability of reference values may be useful in clinical practice and research.

Airway responses to methacholine and exercise at high altitude in healthy lowlanders.

Peribronchial edema has been proposed as a mechanism enhancing airway responses to constrictor stimuli. Acute exposure to altitude in nonacclimatized lowlanders leads to subclinical interstitial pulmonary edema that lasts for several days after ascent, as suggested by changes in lung mechanics. We, therefore, investigated whether changes in lung mechanics consistent with fluid accumulation at high altitude within the lungs are associated with changes in airway responses to methacholine or exercise. Fourteen healthy subjects were studied at 4,559 and at 120 m above sea level. At high altitude, both static and dynamic lung compliances and respiratory reactance at 5 Hz significantly decreased, suggestive of interstitial pulmonary edema. Resting minute ventilation significantly increased by approximately 30%. Compared with sea level, inhalation of methacholine at high altitude caused a similar reduction of partial forced expiratory flow but less reduction of maximal forced expiratory flow, less increments of pulmonary resistance and respiratory resistance at 5 Hz, and similar effects of deep breath on pulmonary and respiratory resistance. During maximal incremental exercise at high altitude, partial forced expiratory flow gradually increased with the increase in minute ventilation similarly to sea level but both achieved higher values at peak exercise. In conclusion, airway responsiveness to methacholine at high altitude is well preserved despite the occurrence of interstitial pulmonary edema. We suggest that this may be the result of the increase in resting minute ventilation opposing the effects and/or the development of airway smooth muscle force, reduced gas density, and well preserved airway-to-parenchyma interdependence.

The hypoxic profile during trekking to the Pyramid Laboratory.

UNLABELLED: The oxygen saturation values reported in the high altitude literature are usually taken during a few minutes of measurement either at rest or during exercise. We aimed to investigate the daily hypoxic profile by monitoring oxygen saturation for 24 h in 8 lowlanders (4 females, ages 26 to 59) during trekking from Lukla (2850 m) to the Pyramid Laboratory (5050 m). Oxygen saturation was measured (1) daily at each altitude (sm), (2) for 24-h during ascent to 3500 m, 4200 m, and on day 1 at 5050 m (lm), and (3) during a standardized exercise (em). RESULTS: (1) the sm and lm values were 90.9% (+/-0.5) and 86.4% (+/-1.1) at 3500 m; 85.2%(+/-1.1), and 80% (+/-1.9) at 4200 m; 83.8%(+/-1) and 77% (+/-1.7) at 5050 m (p < or = 0.05); (2) the daily time spent with oxygen saturation < or =90% was 56.5% at 3500 m, 81% at 4200 m, and 95.5% at 5050 m; (3) during exercise, oxygen saturation decreased by 10.58%, 13.43%, and 11.24% at 3500, 4200, and 5050 m, respectively. In conclusion, our data show that the level of hypoxemia during trekking at altitude is more severe than expected on the basis of a short evaluation at rest and should be taken into account.

Relationship between individual ventilatory response and acute renal water excretion at high altitude.

We tested the hypothesis that the individual ventilatory adaptation to high altitude (HA, 5050 m) may influence renal water excretion in response to water loading. In 8 healthy humans (33+/-4 S.D. years) we studied, at sea level (SL) and at HA, resting ventilation (VE), arterial oxygen saturation (SpO2), urinary output after water loading (WL, 20 mL/kg), and total body water (TBW). Ventilatory response to HA was defined as the difference in resting VE over SpO2 (DeltaVE/DeltaSpO2) from SL to HA. At HA, a significant increase in urinary volume after the first hour from WL (%WLt0-60) was observed. Significant correlations were found between DeltaVE/DeltaSpO2 versus %WLt0-60 at HA and versus changes in TBW, from SL to HA. In conclusion, in healthy subjects the ventilatory response to HA influences water balance and correlates with kidney response to WL. A higher ventilatory response at HA, allowing a more efficient water renal handling, is likely to be a protective mechanisms from altitude illness.

Glottic tuberculosis masquerading as early multifocal carcinoma.

The incidence of tuberculosis has progressively decreased in developed countries after the advent of antituberculous chemotherapy, but has recently been increasing again mainly due to migratory flows. Although common in the past and considered to be a prelethal event, laryngeal involvement has become a rarity. We report the case of a 52-year-old female smoker who complained of persistent aphonia. Videostroboscopy showed bilateral vocal fold erythroleukoplakias. A chest X-ray and CT scan aroused the suspicion of lung tuberculosis, which was confirmed by Ziehl-Neelsen staining for acid-alcohol-fast bacilli on bronchoalveolar lavage. Antituberculous chemotherapy rapidly improved the quality of her voice and led to complete disappearance of the vocal fold lesions. In conclusion, laryngeal tuberculosis may mimic an early glottic multifocal carcinoma and should therefore, despite its rarity, always be considered in the differential diagnosis of erythroleukoplakia-like lesions in order to avoid improper surgical treatment and voice damage.

Airway resistance and airflow dynamics after fat injection into vocal folds.

OBJECTIVES: The aim of this prospective study was to verify whether vocal fold fat augmentation (VFFA) modifies upper airway patency. To the best of our knowledge, this is the first study analyzing the impact of VFFA on laryngeal resistance to airflow. METHODS: Twenty-one consecutive patients 16 to 74 years of age underwent 24 VFFA operations because of glottic incompetence due to laryngeal hemiplegia (13 patients) or vocal fold tissue defects (8 patients). Flow-volume loop spirometry and body plethysmography were performed before and 1 to 6 months after surgery. RESULTS: There were no significant differences between preoperative and postoperative pulmonary volumes (FVC and FEV1), expiratory flows (PEF, FEF50), or inspiratory flows (PIF, FIF50), although a slight increase in inspiratory flows meant that FEF50/FIF50 slightly decreased. Specific airway resistance (sRaw) increased after VFFA, but not in a statistically significant manner (p = .078). None of the patients experienced postoperative stridor. One obese woman with laryngeal hemiplegia had postoperative effort dyspnea; her respiratory studies showed a reduction in inspiratory flows and an increase in sRaw, and demonstrated progressive improvement. CONCLUSIONS: Flow-volume loop spirometry showed that VFFA does not significantly modify respiratory airflows, although a slight increase of inspiratory airflows suggested an improvement in variable extrathoracic obstruction. Body plethysmography proved to be a sensitive procedure that highlighted the subtle increase in upper airway resistance. Hence, VFFA can be considered a relatively safe procedure for achieving vocal fold medialization, and spirometry and plethysmography can be useful for preoperative assessment and postoperative follow-up.

Variability of specific airway resistance in patients with laryngeal hemiplegia.

OBJECTIVES: This study was designed to analyze whether respiratory flows and specific airway resistance (sRaw) depend on the degree of breathiness and on the position of the paralyzed vocal fold in laryngeal hemiplegia. METHODS: We performed a prospective study involving 55 patients affected by laryngeal hemiplegia. RESULTS: The paralyzed fold was in an intermediate position in 18 cases and in a paramedian position in 37. Breathiness was estimated with the GRBAS scale, and the patients were divided into four groups: B0 (12 patients), B1 (14), B2 (16), and B3 (13). Spirometry was used to measure the flow-volume loop, and body plethysmography was used to measure the sRaw at increasing respiratory frequencies (30 +/- 5, 60 +/- 5, and 90 +/- 5 breaths per minute). The mean inspiratory flows (PIF, FIF50) were lower than predicted (<80%) in all four groups; there was no significant intergroup difference. In all four groups, the mean FEF5o/FIF50 ratio was >1, as is typical of variable extrathoracic obstruction. The mean sRaw values increased with respiratory frequency, and the increase was higher in group B3, although the values varied widely. The frequency-dependent increase in the sRaw value was not significantly related to the degree of breathiness, nor to the position of the paralyzed fold. Furthermore, Spearman's coefficient did not reveal any correlation between the sRaw values and inspiratory flows, showing that plethysmography and spirometry explore different aspects of airway function. CONCLUSIONS: Respiratory flows and sRaw are not significantly influenced by either the degree of breathiness or the position of the paralyzed vocal fold.

Spirometric and plethysmographic assessment of upper airway obstruction in laryngeal hemiplegia.

Laryngeal hemiplegia (LH) is the most common disorder of laryngeal motility. It is deemed not to cause obstruction of the upper airway; in fact, the main symptoms are dysphonia and breathiness, and respiratory impairment is not commonly reported. The aim of this study was to objectively assess upper airway patency in 41 patients affected by LH (mean age, 54.4 +/- 15.2 years; 27 female) and 30 controls (mean age, 50.0 +/- 16.1 years; 19 female) by means of flow-volume loop spirometry and body plethysmography to measure specific airway resistance (sRaw) at increasing respiratory frequencies. The causes of LH were cervical surgery (28), tumor infiltration (5), and unexplained (8). None of the patients or controls was affected by lower airway disease. Spirometry showed that the patients had inspiratory flows (PIF, FIF50) significantly lower than those of the controls (p < .0001), whereas the expiratory flows (FEV1, FEF50) were normal, with the exception of peak expiratory flow (PEF), which was reduced, especially in female patients. The mean FEF50/FIF50 ratio (about unity in the normal subjects) was >1, as is typical of variable extrathoracic obstruction. Plethysmography showed that the values of sRaw of the LH group were not statistically different from those of the controls at 30 +/- 5 breaths per minute, but they progressively and significantly increased at 60 +/- 5 (p < .01) and 90 +/- 5 breaths per minute (p < .002), whereas no significant sRaw change was observed in the controls. These results show that LH causes obstruction of the upper airway that can be assessed and quantified by means of spirometry and body plethysmography. A dynamic narrowing due to inspiratory medialization of the paralytic vocal fold and flow turbulence during hyperventilation seem to be the causes of patency impairment. The flow-volume loop is an excellent, inexpensive, and easily available means of functionally evaluating upper airway obstruction, but some patients have difficulty in performing an inspiratory test that requires maximal effort, and the flow reduction during forced ventilation may be partially due to the effort dependency of the tests themselves. Plethysmographic assessment of airway resistance may be a valid alternative or complement, as it reveals an increase in sRaw at increasing respiratory frequencies.