**2. Evaluation of pulmonary function**

As already mentioned, when patients with ALS seek medical attention, they do not usually display signs of pulmonary involvement, and do not refer respiratory complaints. However, during the progression of the disease all patients eventually complain of dyspnea with exertion, orthopnea, and poor sleep quality with frequent awakenings, nightmares, early morning headaches or excessive daytime sleepiness (Heffernan et al., 2006; Beneditt & Boitano, 2008). A clinical examination at this point might show respiratory paradox, rapid shallow breathing or accessory muscle contraction. Nevertheless, the observation that many patients may remain asymptomatic even when there is a marked reduction of vital capacity limits the reliability of these signs and symptoms. There are, however, several dyspnea rating scales, such as the Borg dyspnoea score, the baseline dyspnea index and the transition dyspnea index, that have been recently reconsidered and their implementation has been encouraged (Lechtzin et al., 2007a; Just et al., 2010).

In addition to respiratory symptoms and signs, many exams are used in the evaluation of pulmonary function in patients with ALS (Heffernan et al., 2006; Beneditt & Boitano, 2008; Lo Coco et al., 2008; Miller et al., 2009a).

The most widely available measure for detecting respiratory decline is forced vital capacity (FVC) sitting and/or supine. FVC is correlated with survival, and usually presents an almost linear decrease during the course of the disease, but with a marked variability from patient to patient (within 2% to 4% of predicted value per month) (Fallat et al., 1979; Munsat et al., 1988; Schiffman & Belsh, 1993; Stembler et al., 1998; Czaplinski et al., 2006; Lo Coco et al., 2006a).

FVC, however, has some well known limitations, such as low sensitiveness in patients with bulbar involvement, because of reduced buccal strength, or cognitive involvement, and a relative insensitiveness to detect mild or moderate diaphragmatic dysfunction. According to many specialists, supine FVC, although more difficult to perform, has superior sensitivity over seated FVC in predicting survival, is closely correlated with transdiaphragmatic pressure, and then should be always executed in the evaluation of patients with ALS (Varrato et al., 2001; Schmidt et al., 2006; Baumann et al., 2010).

Maximal inspiratory and expiratory pressure (MIP and MEP) are other sensitive measurements, and it has been shown that many patients with an FVC > 70% had abnormal MIP (< -60 cm) (Jackson et al., 2001). However, since many patients are unable to perform the test with the progression of disease, in many centres these two tests are not routinely executed.

major issue in the multidisciplinary assessment of patients with ALS, and the pulmonologist has gained an increasing role in this process. However, there is still little consensus on pulmonary care worldwide, and clinical practice varies widely from country to country, especially when NIPPV becomes inadequate to support respiratory muscle failure. It is, then, good practice to discuss respiratory issues in advance with the patients and their carers in order to avoid emergency interventions or unwanted treatments, and frequently

This chapter focuses on the recent advances that have emerged in the management of pulmonary dysfunction in patients with ALS with emphasis on respiratory evaluation and

As already mentioned, when patients with ALS seek medical attention, they do not usually display signs of pulmonary involvement, and do not refer respiratory complaints. However, during the progression of the disease all patients eventually complain of dyspnea with exertion, orthopnea, and poor sleep quality with frequent awakenings, nightmares, early morning headaches or excessive daytime sleepiness (Heffernan et al., 2006; Beneditt & Boitano, 2008). A clinical examination at this point might show respiratory paradox, rapid shallow breathing or accessory muscle contraction. Nevertheless, the observation that many patients may remain asymptomatic even when there is a marked reduction of vital capacity limits the reliability of these signs and symptoms. There are, however, several dyspnea rating scales, such as the Borg dyspnoea score, the baseline dyspnea index and the transition dyspnea index, that have been recently reconsidered and their implementation has been

In addition to respiratory symptoms and signs, many exams are used in the evaluation of pulmonary function in patients with ALS (Heffernan et al., 2006; Beneditt & Boitano, 2008;

The most widely available measure for detecting respiratory decline is forced vital capacity (FVC) sitting and/or supine. FVC is correlated with survival, and usually presents an almost linear decrease during the course of the disease, but with a marked variability from patient to patient (within 2% to 4% of predicted value per month) (Fallat et al., 1979; Munsat et al., 1988; Schiffman & Belsh, 1993; Stembler et al., 1998; Czaplinski et al., 2006; Lo Coco et

FVC, however, has some well known limitations, such as low sensitiveness in patients with bulbar involvement, because of reduced buccal strength, or cognitive involvement, and a relative insensitiveness to detect mild or moderate diaphragmatic dysfunction. According to many specialists, supine FVC, although more difficult to perform, has superior sensitivity over seated FVC in predicting survival, is closely correlated with transdiaphragmatic pressure, and then should be always executed in the evaluation of patients with ALS

Maximal inspiratory and expiratory pressure (MIP and MEP) are other sensitive measurements, and it has been shown that many patients with an FVC > 70% had abnormal MIP (< -60 cm) (Jackson et al., 2001). However, since many patients are unable to perform the test with the progression of disease, in many centres these two tests are not routinely

review these decisions during the course of the disease.

**2. Evaluation of pulmonary function** 

encouraged (Lechtzin et al., 2007a; Just et al., 2010).

(Varrato et al., 2001; Schmidt et al., 2006; Baumann et al., 2010).

Lo Coco et al., 2008; Miller et al., 2009a).

al., 2006a).

executed.

mechanical ventilation.

Arterial blood gas analysis may also be of help in the evaluation of patients with ALS, especially in those with severe bulbar involvement, since it could reveal resting hypercapnia (PaCO2 > 6.5 kPa) and/or hypoxemia (PaO2 < 80 mmHg). However, these are usually very late signs of respiratory failure in ALS.

Sniff nasal inspiratory pressure (SNIP) is regarded as a good measure of diaphragmatic strength, and is probably more accurate than FVC, especially at later stages, although even SNIP may underestimate respiratory function in patients with bulbar involvement, because of upper airway collapse. However, a sniff nasal pressure test < 40% of predicted value (or < 60 cmH2O) is a significant predictor of sleep disordered breathing, nocturnal hypoxemia, hypercapnia and mortality (Fitting et al., 1999; Lyall et al., 2001b; Carrat et al., 2011).

Finally, nocturnal hypoventilation and sleep-disordered breathing are common problems in ALS with the progression of the disease, and can occur even when respiratory muscle function is only mildly affected and in the presence of normal daytime gas exchange (Gay et al., 1991; Ferguson et al., 1996; Arnulf et al., 2000). Nocturnal hypoventilation is particularly severe during rapid eye movements (REM) sleep, when all postural and accessory muscles are physiologically atonic, and only the diaphragm, which may itself be impaired, is left to sustain ventilation and overcome any upper airway resistance (Ferguson et al., 1996). Then, since nocturnal oximetry is easily performed and can be executed domiciliary, it has become frequently used in clinical practice for the evaluation of respiratory involvement in patients with ALS and as a guide to initiate mechanical ventilation. Nocturnal oximetry correlated with survival (mean SaO2 < 93 mmHg was associated with mean survival of 7 months vs 18 months when mean SaO2 > 93 mmHg) (Velasco et al., 2002), and nocturnal desaturations < 90% for 1 cumulative minute was a more sensitive indicator of nocturnal hypoventilation than either FVC or MIP (Jackson et al., 2001). Polysomnography is not routinely performed, because is costly and demanding, although it can reveal causes of poor sleep quality different from disordered breathing, such as motor activity during sleep (Lo Coco et al., 2011).
